|
Cytotoxicity against human A549 lung tumor cells
|
Homo sapiens
|
0.0013
ug.mL-1
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Semisynthesis of C-ring modified triptolide analogues and their cytotoxic activities.
Year : 2006
Volume : 16
Issue : 7
First Page : 1947
Last Page : 1949
Authors : Aoyagi Y, Hitotsuyanagi Y, Hasuda T, Fukaya H, Takeya K, Aiyama R, Matsuzaki T, Hashimoto S.
Abstract : Several C-ring modified analogues of a potent antileukemic diterpene, triptolide (1), were synthesized and their structure-activity relationships were studied.
|
Cytotoxicity against human HT29 colon tumor cells
|
Homo sapiens
|
0.0001
ug.mL-1
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Semisynthesis of C-ring modified triptolide analogues and their cytotoxic activities.
Year : 2006
Volume : 16
Issue : 7
First Page : 1947
Last Page : 1949
Authors : Aoyagi Y, Hitotsuyanagi Y, Hasuda T, Fukaya H, Takeya K, Aiyama R, Matsuzaki T, Hashimoto S.
Abstract : Several C-ring modified analogues of a potent antileukemic diterpene, triptolide (1), were synthesized and their structure-activity relationships were studied.
|
Cytotoxicity against human A549 cells
|
Homo sapiens
|
0.0013
ug.mL-1
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Fluorination of triptolide and its analogues and their cytotoxicity.
Year : 2008
Volume : 18
Issue : 7
First Page : 2459
Last Page : 2463
Authors : Aoyagi Y, Hitotsuyanagi Y, Hasuda T, Matsuyama S, Fukaya H, Takeya K, Aiyama R, Matsuzaki T, Hashimoto S.
Abstract : The reaction of triptolide and its analogues with a fluorinating agent, that is, bis(2-methoxyethyl)aminosulfur trifluoride (Deoxo-Fluor) or (diethylamino)sulfur trifluoride (DAST), was studied. One of the fluorinated products, 14beta-dehydroxy-14beta-fluoro triptolide, was found to be more cytotoxic than the parent natural triptolide.
|
Cytotoxicity against human HT29 cells
|
Homo sapiens
|
0.0001
ug.mL-1
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Fluorination of triptolide and its analogues and their cytotoxicity.
Year : 2008
Volume : 18
Issue : 7
First Page : 2459
Last Page : 2463
Authors : Aoyagi Y, Hitotsuyanagi Y, Hasuda T, Matsuyama S, Fukaya H, Takeya K, Aiyama R, Matsuzaki T, Hashimoto S.
Abstract : The reaction of triptolide and its analogues with a fluorinating agent, that is, bis(2-methoxyethyl)aminosulfur trifluoride (Deoxo-Fluor) or (diethylamino)sulfur trifluoride (DAST), was studied. One of the fluorinated products, 14beta-dehydroxy-14beta-fluoro triptolide, was found to be more cytotoxic than the parent natural triptolide.
|
Inhibition of COX2
|
None
|
40.0
nM
|
|
Journal : J. Nat. Prod.
Title : Expanding the ChemGPS chemical space with natural products.
Year : 2005
Volume : 68
Issue : 7
First Page : 985
Last Page : 991
Authors : Larsson J, Gottfries J, Bohlin L, Backlund A.
Abstract : Recently various attempts have been made to increase the efficacy and precision of chemical libraries used in high-throughput screening (HTS) drug discovery approaches. One such approach is ChemGPS, which provides a defined chemical space for prescreening evaluation of chemical compound properties or virtual dereplication. In the present study, ChemGPS has been applied to a set of natural products shown to exhibit cyclooxygenase-1 and/or -2 (COX-1/2) inhibition. With the purpose of defining chemical properties and linking these to the observed mode of enzyme inhibition, this resulted in two lines of reasoning. On one hand several specific features of these compounds have been identified and discussed. Overall COX inhibition was frequently correlated with the presence of at least one ring in the structure, fragments exhibiting structural rigidity, and a relatively large molecular size. The concept "size" includes several parameters, e.g., molecular volume, weight, and number of bonds. On the other hand, and possibly even more important, was the unexpected finding that the natural products studied to a large extent fell outside the defined ChemGPS chemical space. Therefore, we also propose an expanded space for natural products: ChemGPS-NP.
|
Cytotoxicity against human SGC7901 cells after 72 hrs by MTT assay
|
Homo sapiens
|
15.0
nM
|
|
Journal : J. Med. Chem.
Title : Design and synthesis of novel C14-hydroxyl substituted triptolide derivatives as potential selective antitumor agents.
Year : 2009
Volume : 52
Issue : 16
First Page : 5115
Last Page : 5123
Authors : Li Z, Zhou ZL, Miao ZH, Lin LP, Feng HJ, Tong LJ, Ding J, Li YC.
Abstract : It has long been considered that the free beta hydroxyl group at C14 of triptolide (1) is essential to its potent anticancer activity. In this study, we synthesized novel derivatives of 1 with a hydroxyl group substituted by epoxy groups (4-8) or a five-membered ring (11-13). Compounds (4-8) showed significant in vitro anticancer activity although less potent than 1. Although with an alpha oxygen configuration at the C14 position, (14S)-14,21-epoxytriptolide (4) exhibited the highest potency among all these derivatives, clearly challenging the traditional viewpoint on the necessity of C14beta-hydroxyl group of compound 1. Further studies revealed that while displaying broad spectrum in vitro anticancer activity, compound 4 demonstrated prominent selective in vivo anticancer activity, particularly against human ovarian SK-OV-3 and prostate PC-3 cancers with obviously lower toxicity than 1. Noticeably, compound 4 was also highly effective against multidrug resistant cancer cells. Therefore, our study gives new insights into the structure-activity relationship of 1 and also produces a promising anticancer drug candidate with unique anticancer activities.
|
Cytotoxicity against human A549 cells after 72 hrs by MTT assay
|
Homo sapiens
|
59.0
nM
|
|
Journal : J. Med. Chem.
Title : Design and synthesis of novel C14-hydroxyl substituted triptolide derivatives as potential selective antitumor agents.
Year : 2009
Volume : 52
Issue : 16
First Page : 5115
Last Page : 5123
Authors : Li Z, Zhou ZL, Miao ZH, Lin LP, Feng HJ, Tong LJ, Ding J, Li YC.
Abstract : It has long been considered that the free beta hydroxyl group at C14 of triptolide (1) is essential to its potent anticancer activity. In this study, we synthesized novel derivatives of 1 with a hydroxyl group substituted by epoxy groups (4-8) or a five-membered ring (11-13). Compounds (4-8) showed significant in vitro anticancer activity although less potent than 1. Although with an alpha oxygen configuration at the C14 position, (14S)-14,21-epoxytriptolide (4) exhibited the highest potency among all these derivatives, clearly challenging the traditional viewpoint on the necessity of C14beta-hydroxyl group of compound 1. Further studies revealed that while displaying broad spectrum in vitro anticancer activity, compound 4 demonstrated prominent selective in vivo anticancer activity, particularly against human ovarian SK-OV-3 and prostate PC-3 cancers with obviously lower toxicity than 1. Noticeably, compound 4 was also highly effective against multidrug resistant cancer cells. Therefore, our study gives new insights into the structure-activity relationship of 1 and also produces a promising anticancer drug candidate with unique anticancer activities.
|
Cytotoxicity against human K562 cells after 72 hrs by MTT assay
|
Homo sapiens
|
50.0
nM
|
|
Journal : J. Med. Chem.
Title : Design and synthesis of novel C14-hydroxyl substituted triptolide derivatives as potential selective antitumor agents.
Year : 2009
Volume : 52
Issue : 16
First Page : 5115
Last Page : 5123
Authors : Li Z, Zhou ZL, Miao ZH, Lin LP, Feng HJ, Tong LJ, Ding J, Li YC.
Abstract : It has long been considered that the free beta hydroxyl group at C14 of triptolide (1) is essential to its potent anticancer activity. In this study, we synthesized novel derivatives of 1 with a hydroxyl group substituted by epoxy groups (4-8) or a five-membered ring (11-13). Compounds (4-8) showed significant in vitro anticancer activity although less potent than 1. Although with an alpha oxygen configuration at the C14 position, (14S)-14,21-epoxytriptolide (4) exhibited the highest potency among all these derivatives, clearly challenging the traditional viewpoint on the necessity of C14beta-hydroxyl group of compound 1. Further studies revealed that while displaying broad spectrum in vitro anticancer activity, compound 4 demonstrated prominent selective in vivo anticancer activity, particularly against human ovarian SK-OV-3 and prostate PC-3 cancers with obviously lower toxicity than 1. Noticeably, compound 4 was also highly effective against multidrug resistant cancer cells. Therefore, our study gives new insights into the structure-activity relationship of 1 and also produces a promising anticancer drug candidate with unique anticancer activities.
|
Cytotoxicity against human MOLT4 cells after 72 hrs by MTT assay
|
Homo sapiens
|
17.0
nM
|
|
Journal : J. Med. Chem.
Title : Design and synthesis of novel C14-hydroxyl substituted triptolide derivatives as potential selective antitumor agents.
Year : 2009
Volume : 52
Issue : 16
First Page : 5115
Last Page : 5123
Authors : Li Z, Zhou ZL, Miao ZH, Lin LP, Feng HJ, Tong LJ, Ding J, Li YC.
Abstract : It has long been considered that the free beta hydroxyl group at C14 of triptolide (1) is essential to its potent anticancer activity. In this study, we synthesized novel derivatives of 1 with a hydroxyl group substituted by epoxy groups (4-8) or a five-membered ring (11-13). Compounds (4-8) showed significant in vitro anticancer activity although less potent than 1. Although with an alpha oxygen configuration at the C14 position, (14S)-14,21-epoxytriptolide (4) exhibited the highest potency among all these derivatives, clearly challenging the traditional viewpoint on the necessity of C14beta-hydroxyl group of compound 1. Further studies revealed that while displaying broad spectrum in vitro anticancer activity, compound 4 demonstrated prominent selective in vivo anticancer activity, particularly against human ovarian SK-OV-3 and prostate PC-3 cancers with obviously lower toxicity than 1. Noticeably, compound 4 was also highly effective against multidrug resistant cancer cells. Therefore, our study gives new insights into the structure-activity relationship of 1 and also produces a promising anticancer drug candidate with unique anticancer activities.
|
Cytotoxicity against human PC3 cells by SRB assay
|
Homo sapiens
|
20.0
nM
|
|
Journal : J. Med. Chem.
Title : Design and synthesis of novel C14-hydroxyl substituted triptolide derivatives as potential selective antitumor agents.
Year : 2009
Volume : 52
Issue : 16
First Page : 5115
Last Page : 5123
Authors : Li Z, Zhou ZL, Miao ZH, Lin LP, Feng HJ, Tong LJ, Ding J, Li YC.
Abstract : It has long been considered that the free beta hydroxyl group at C14 of triptolide (1) is essential to its potent anticancer activity. In this study, we synthesized novel derivatives of 1 with a hydroxyl group substituted by epoxy groups (4-8) or a five-membered ring (11-13). Compounds (4-8) showed significant in vitro anticancer activity although less potent than 1. Although with an alpha oxygen configuration at the C14 position, (14S)-14,21-epoxytriptolide (4) exhibited the highest potency among all these derivatives, clearly challenging the traditional viewpoint on the necessity of C14beta-hydroxyl group of compound 1. Further studies revealed that while displaying broad spectrum in vitro anticancer activity, compound 4 demonstrated prominent selective in vivo anticancer activity, particularly against human ovarian SK-OV-3 and prostate PC-3 cancers with obviously lower toxicity than 1. Noticeably, compound 4 was also highly effective against multidrug resistant cancer cells. Therefore, our study gives new insights into the structure-activity relationship of 1 and also produces a promising anticancer drug candidate with unique anticancer activities.
|
Cytotoxicity against human MDA-MB-468 cells by SRB assay
|
Homo sapiens
|
10.0
nM
|
|
Journal : J. Med. Chem.
Title : Design and synthesis of novel C14-hydroxyl substituted triptolide derivatives as potential selective antitumor agents.
Year : 2009
Volume : 52
Issue : 16
First Page : 5115
Last Page : 5123
Authors : Li Z, Zhou ZL, Miao ZH, Lin LP, Feng HJ, Tong LJ, Ding J, Li YC.
Abstract : It has long been considered that the free beta hydroxyl group at C14 of triptolide (1) is essential to its potent anticancer activity. In this study, we synthesized novel derivatives of 1 with a hydroxyl group substituted by epoxy groups (4-8) or a five-membered ring (11-13). Compounds (4-8) showed significant in vitro anticancer activity although less potent than 1. Although with an alpha oxygen configuration at the C14 position, (14S)-14,21-epoxytriptolide (4) exhibited the highest potency among all these derivatives, clearly challenging the traditional viewpoint on the necessity of C14beta-hydroxyl group of compound 1. Further studies revealed that while displaying broad spectrum in vitro anticancer activity, compound 4 demonstrated prominent selective in vivo anticancer activity, particularly against human ovarian SK-OV-3 and prostate PC-3 cancers with obviously lower toxicity than 1. Noticeably, compound 4 was also highly effective against multidrug resistant cancer cells. Therefore, our study gives new insights into the structure-activity relationship of 1 and also produces a promising anticancer drug candidate with unique anticancer activities.
|
Cytotoxicity against human SKOV3 cells by SRB assay
|
Homo sapiens
|
9.0
nM
|
|
Journal : J. Med. Chem.
Title : Design and synthesis of novel C14-hydroxyl substituted triptolide derivatives as potential selective antitumor agents.
Year : 2009
Volume : 52
Issue : 16
First Page : 5115
Last Page : 5123
Authors : Li Z, Zhou ZL, Miao ZH, Lin LP, Feng HJ, Tong LJ, Ding J, Li YC.
Abstract : It has long been considered that the free beta hydroxyl group at C14 of triptolide (1) is essential to its potent anticancer activity. In this study, we synthesized novel derivatives of 1 with a hydroxyl group substituted by epoxy groups (4-8) or a five-membered ring (11-13). Compounds (4-8) showed significant in vitro anticancer activity although less potent than 1. Although with an alpha oxygen configuration at the C14 position, (14S)-14,21-epoxytriptolide (4) exhibited the highest potency among all these derivatives, clearly challenging the traditional viewpoint on the necessity of C14beta-hydroxyl group of compound 1. Further studies revealed that while displaying broad spectrum in vitro anticancer activity, compound 4 demonstrated prominent selective in vivo anticancer activity, particularly against human ovarian SK-OV-3 and prostate PC-3 cancers with obviously lower toxicity than 1. Noticeably, compound 4 was also highly effective against multidrug resistant cancer cells. Therefore, our study gives new insights into the structure-activity relationship of 1 and also produces a promising anticancer drug candidate with unique anticancer activities.
|
Cytotoxicity against human MKN28 cells after 72 hrs by MTT assay
|
Homo sapiens
|
200.0
nM
|
|
Journal : J. Med. Chem.
Title : Design and synthesis of novel C14-hydroxyl substituted triptolide derivatives as potential selective antitumor agents.
Year : 2009
Volume : 52
Issue : 16
First Page : 5115
Last Page : 5123
Authors : Li Z, Zhou ZL, Miao ZH, Lin LP, Feng HJ, Tong LJ, Ding J, Li YC.
Abstract : It has long been considered that the free beta hydroxyl group at C14 of triptolide (1) is essential to its potent anticancer activity. In this study, we synthesized novel derivatives of 1 with a hydroxyl group substituted by epoxy groups (4-8) or a five-membered ring (11-13). Compounds (4-8) showed significant in vitro anticancer activity although less potent than 1. Although with an alpha oxygen configuration at the C14 position, (14S)-14,21-epoxytriptolide (4) exhibited the highest potency among all these derivatives, clearly challenging the traditional viewpoint on the necessity of C14beta-hydroxyl group of compound 1. Further studies revealed that while displaying broad spectrum in vitro anticancer activity, compound 4 demonstrated prominent selective in vivo anticancer activity, particularly against human ovarian SK-OV-3 and prostate PC-3 cancers with obviously lower toxicity than 1. Noticeably, compound 4 was also highly effective against multidrug resistant cancer cells. Therefore, our study gives new insights into the structure-activity relationship of 1 and also produces a promising anticancer drug candidate with unique anticancer activities.
|
Cytotoxicity against human HCT116 cells after 72 hrs by MTT assay
|
Homo sapiens
|
10.0
nM
|
|
Journal : J. Med. Chem.
Title : Design and synthesis of novel C14-hydroxyl substituted triptolide derivatives as potential selective antitumor agents.
Year : 2009
Volume : 52
Issue : 16
First Page : 5115
Last Page : 5123
Authors : Li Z, Zhou ZL, Miao ZH, Lin LP, Feng HJ, Tong LJ, Ding J, Li YC.
Abstract : It has long been considered that the free beta hydroxyl group at C14 of triptolide (1) is essential to its potent anticancer activity. In this study, we synthesized novel derivatives of 1 with a hydroxyl group substituted by epoxy groups (4-8) or a five-membered ring (11-13). Compounds (4-8) showed significant in vitro anticancer activity although less potent than 1. Although with an alpha oxygen configuration at the C14 position, (14S)-14,21-epoxytriptolide (4) exhibited the highest potency among all these derivatives, clearly challenging the traditional viewpoint on the necessity of C14beta-hydroxyl group of compound 1. Further studies revealed that while displaying broad spectrum in vitro anticancer activity, compound 4 demonstrated prominent selective in vivo anticancer activity, particularly against human ovarian SK-OV-3 and prostate PC-3 cancers with obviously lower toxicity than 1. Noticeably, compound 4 was also highly effective against multidrug resistant cancer cells. Therefore, our study gives new insights into the structure-activity relationship of 1 and also produces a promising anticancer drug candidate with unique anticancer activities.
|
Cytotoxicity against human SW1116 cells after 72 hrs by MTT assay
|
Homo sapiens
|
52.0
nM
|
|
Journal : J. Med. Chem.
Title : Design and synthesis of novel C14-hydroxyl substituted triptolide derivatives as potential selective antitumor agents.
Year : 2009
Volume : 52
Issue : 16
First Page : 5115
Last Page : 5123
Authors : Li Z, Zhou ZL, Miao ZH, Lin LP, Feng HJ, Tong LJ, Ding J, Li YC.
Abstract : It has long been considered that the free beta hydroxyl group at C14 of triptolide (1) is essential to its potent anticancer activity. In this study, we synthesized novel derivatives of 1 with a hydroxyl group substituted by epoxy groups (4-8) or a five-membered ring (11-13). Compounds (4-8) showed significant in vitro anticancer activity although less potent than 1. Although with an alpha oxygen configuration at the C14 position, (14S)-14,21-epoxytriptolide (4) exhibited the highest potency among all these derivatives, clearly challenging the traditional viewpoint on the necessity of C14beta-hydroxyl group of compound 1. Further studies revealed that while displaying broad spectrum in vitro anticancer activity, compound 4 demonstrated prominent selective in vivo anticancer activity, particularly against human ovarian SK-OV-3 and prostate PC-3 cancers with obviously lower toxicity than 1. Noticeably, compound 4 was also highly effective against multidrug resistant cancer cells. Therefore, our study gives new insights into the structure-activity relationship of 1 and also produces a promising anticancer drug candidate with unique anticancer activities.
|
Cytotoxicity against human HCT15 cells after 72 hrs by MTT assay
|
Homo sapiens
|
29.0
nM
|
|
Journal : J. Med. Chem.
Title : Design and synthesis of novel C14-hydroxyl substituted triptolide derivatives as potential selective antitumor agents.
Year : 2009
Volume : 52
Issue : 16
First Page : 5115
Last Page : 5123
Authors : Li Z, Zhou ZL, Miao ZH, Lin LP, Feng HJ, Tong LJ, Ding J, Li YC.
Abstract : It has long been considered that the free beta hydroxyl group at C14 of triptolide (1) is essential to its potent anticancer activity. In this study, we synthesized novel derivatives of 1 with a hydroxyl group substituted by epoxy groups (4-8) or a five-membered ring (11-13). Compounds (4-8) showed significant in vitro anticancer activity although less potent than 1. Although with an alpha oxygen configuration at the C14 position, (14S)-14,21-epoxytriptolide (4) exhibited the highest potency among all these derivatives, clearly challenging the traditional viewpoint on the necessity of C14beta-hydroxyl group of compound 1. Further studies revealed that while displaying broad spectrum in vitro anticancer activity, compound 4 demonstrated prominent selective in vivo anticancer activity, particularly against human ovarian SK-OV-3 and prostate PC-3 cancers with obviously lower toxicity than 1. Noticeably, compound 4 was also highly effective against multidrug resistant cancer cells. Therefore, our study gives new insights into the structure-activity relationship of 1 and also produces a promising anticancer drug candidate with unique anticancer activities.
|
Cytotoxicity against human SMMC7721 cells after 72 hrs by MTT assay
|
Homo sapiens
|
18.0
nM
|
|
Journal : J. Med. Chem.
Title : Design and synthesis of novel C14-hydroxyl substituted triptolide derivatives as potential selective antitumor agents.
Year : 2009
Volume : 52
Issue : 16
First Page : 5115
Last Page : 5123
Authors : Li Z, Zhou ZL, Miao ZH, Lin LP, Feng HJ, Tong LJ, Ding J, Li YC.
Abstract : It has long been considered that the free beta hydroxyl group at C14 of triptolide (1) is essential to its potent anticancer activity. In this study, we synthesized novel derivatives of 1 with a hydroxyl group substituted by epoxy groups (4-8) or a five-membered ring (11-13). Compounds (4-8) showed significant in vitro anticancer activity although less potent than 1. Although with an alpha oxygen configuration at the C14 position, (14S)-14,21-epoxytriptolide (4) exhibited the highest potency among all these derivatives, clearly challenging the traditional viewpoint on the necessity of C14beta-hydroxyl group of compound 1. Further studies revealed that while displaying broad spectrum in vitro anticancer activity, compound 4 demonstrated prominent selective in vivo anticancer activity, particularly against human ovarian SK-OV-3 and prostate PC-3 cancers with obviously lower toxicity than 1. Noticeably, compound 4 was also highly effective against multidrug resistant cancer cells. Therefore, our study gives new insights into the structure-activity relationship of 1 and also produces a promising anticancer drug candidate with unique anticancer activities.
|
Cytotoxicity against human Bel7402 cells after 72 hrs by MTT assay
|
Homo sapiens
|
20.0
nM
|
|
Journal : J. Med. Chem.
Title : Design and synthesis of novel C14-hydroxyl substituted triptolide derivatives as potential selective antitumor agents.
Year : 2009
Volume : 52
Issue : 16
First Page : 5115
Last Page : 5123
Authors : Li Z, Zhou ZL, Miao ZH, Lin LP, Feng HJ, Tong LJ, Ding J, Li YC.
Abstract : It has long been considered that the free beta hydroxyl group at C14 of triptolide (1) is essential to its potent anticancer activity. In this study, we synthesized novel derivatives of 1 with a hydroxyl group substituted by epoxy groups (4-8) or a five-membered ring (11-13). Compounds (4-8) showed significant in vitro anticancer activity although less potent than 1. Although with an alpha oxygen configuration at the C14 position, (14S)-14,21-epoxytriptolide (4) exhibited the highest potency among all these derivatives, clearly challenging the traditional viewpoint on the necessity of C14beta-hydroxyl group of compound 1. Further studies revealed that while displaying broad spectrum in vitro anticancer activity, compound 4 demonstrated prominent selective in vivo anticancer activity, particularly against human ovarian SK-OV-3 and prostate PC-3 cancers with obviously lower toxicity than 1. Noticeably, compound 4 was also highly effective against multidrug resistant cancer cells. Therefore, our study gives new insights into the structure-activity relationship of 1 and also produces a promising anticancer drug candidate with unique anticancer activities.
|
Cytotoxicity against human 786-O cells after 72 hrs by MTT assay
|
Homo sapiens
|
22.0
nM
|
|
Journal : J. Med. Chem.
Title : Design and synthesis of novel C14-hydroxyl substituted triptolide derivatives as potential selective antitumor agents.
Year : 2009
Volume : 52
Issue : 16
First Page : 5115
Last Page : 5123
Authors : Li Z, Zhou ZL, Miao ZH, Lin LP, Feng HJ, Tong LJ, Ding J, Li YC.
Abstract : It has long been considered that the free beta hydroxyl group at C14 of triptolide (1) is essential to its potent anticancer activity. In this study, we synthesized novel derivatives of 1 with a hydroxyl group substituted by epoxy groups (4-8) or a five-membered ring (11-13). Compounds (4-8) showed significant in vitro anticancer activity although less potent than 1. Although with an alpha oxygen configuration at the C14 position, (14S)-14,21-epoxytriptolide (4) exhibited the highest potency among all these derivatives, clearly challenging the traditional viewpoint on the necessity of C14beta-hydroxyl group of compound 1. Further studies revealed that while displaying broad spectrum in vitro anticancer activity, compound 4 demonstrated prominent selective in vivo anticancer activity, particularly against human ovarian SK-OV-3 and prostate PC-3 cancers with obviously lower toxicity than 1. Noticeably, compound 4 was also highly effective against multidrug resistant cancer cells. Therefore, our study gives new insights into the structure-activity relationship of 1 and also produces a promising anticancer drug candidate with unique anticancer activities.
|
Cytotoxicity against human MDA-MB-231 cells after 72 hrs by MTT assay
|
Homo sapiens
|
24.0
nM
|
|
Journal : J. Med. Chem.
Title : Design and synthesis of novel C14-hydroxyl substituted triptolide derivatives as potential selective antitumor agents.
Year : 2009
Volume : 52
Issue : 16
First Page : 5115
Last Page : 5123
Authors : Li Z, Zhou ZL, Miao ZH, Lin LP, Feng HJ, Tong LJ, Ding J, Li YC.
Abstract : It has long been considered that the free beta hydroxyl group at C14 of triptolide (1) is essential to its potent anticancer activity. In this study, we synthesized novel derivatives of 1 with a hydroxyl group substituted by epoxy groups (4-8) or a five-membered ring (11-13). Compounds (4-8) showed significant in vitro anticancer activity although less potent than 1. Although with an alpha oxygen configuration at the C14 position, (14S)-14,21-epoxytriptolide (4) exhibited the highest potency among all these derivatives, clearly challenging the traditional viewpoint on the necessity of C14beta-hydroxyl group of compound 1. Further studies revealed that while displaying broad spectrum in vitro anticancer activity, compound 4 demonstrated prominent selective in vivo anticancer activity, particularly against human ovarian SK-OV-3 and prostate PC-3 cancers with obviously lower toxicity than 1. Noticeably, compound 4 was also highly effective against multidrug resistant cancer cells. Therefore, our study gives new insights into the structure-activity relationship of 1 and also produces a promising anticancer drug candidate with unique anticancer activities.
|
Cytotoxicity against human MCF7 cells after 72 hrs by MTT assay
|
Homo sapiens
|
19.0
nM
|
|
Journal : J. Med. Chem.
Title : Design and synthesis of novel C14-hydroxyl substituted triptolide derivatives as potential selective antitumor agents.
Year : 2009
Volume : 52
Issue : 16
First Page : 5115
Last Page : 5123
Authors : Li Z, Zhou ZL, Miao ZH, Lin LP, Feng HJ, Tong LJ, Ding J, Li YC.
Abstract : It has long been considered that the free beta hydroxyl group at C14 of triptolide (1) is essential to its potent anticancer activity. In this study, we synthesized novel derivatives of 1 with a hydroxyl group substituted by epoxy groups (4-8) or a five-membered ring (11-13). Compounds (4-8) showed significant in vitro anticancer activity although less potent than 1. Although with an alpha oxygen configuration at the C14 position, (14S)-14,21-epoxytriptolide (4) exhibited the highest potency among all these derivatives, clearly challenging the traditional viewpoint on the necessity of C14beta-hydroxyl group of compound 1. Further studies revealed that while displaying broad spectrum in vitro anticancer activity, compound 4 demonstrated prominent selective in vivo anticancer activity, particularly against human ovarian SK-OV-3 and prostate PC-3 cancers with obviously lower toxicity than 1. Noticeably, compound 4 was also highly effective against multidrug resistant cancer cells. Therefore, our study gives new insights into the structure-activity relationship of 1 and also produces a promising anticancer drug candidate with unique anticancer activities.
|
Cytotoxicity against human SKOV3 cells after 72 hrs by MTT assay
|
Homo sapiens
|
10.0
nM
|
|
Journal : J. Med. Chem.
Title : Design and synthesis of novel C14-hydroxyl substituted triptolide derivatives as potential selective antitumor agents.
Year : 2009
Volume : 52
Issue : 16
First Page : 5115
Last Page : 5123
Authors : Li Z, Zhou ZL, Miao ZH, Lin LP, Feng HJ, Tong LJ, Ding J, Li YC.
Abstract : It has long been considered that the free beta hydroxyl group at C14 of triptolide (1) is essential to its potent anticancer activity. In this study, we synthesized novel derivatives of 1 with a hydroxyl group substituted by epoxy groups (4-8) or a five-membered ring (11-13). Compounds (4-8) showed significant in vitro anticancer activity although less potent than 1. Although with an alpha oxygen configuration at the C14 position, (14S)-14,21-epoxytriptolide (4) exhibited the highest potency among all these derivatives, clearly challenging the traditional viewpoint on the necessity of C14beta-hydroxyl group of compound 1. Further studies revealed that while displaying broad spectrum in vitro anticancer activity, compound 4 demonstrated prominent selective in vivo anticancer activity, particularly against human ovarian SK-OV-3 and prostate PC-3 cancers with obviously lower toxicity than 1. Noticeably, compound 4 was also highly effective against multidrug resistant cancer cells. Therefore, our study gives new insights into the structure-activity relationship of 1 and also produces a promising anticancer drug candidate with unique anticancer activities.
|
Cytotoxicity against human HO8910 cells after 72 hrs by MTT assay
|
Homo sapiens
|
28.0
nM
|
|
Journal : J. Med. Chem.
Title : Design and synthesis of novel C14-hydroxyl substituted triptolide derivatives as potential selective antitumor agents.
Year : 2009
Volume : 52
Issue : 16
First Page : 5115
Last Page : 5123
Authors : Li Z, Zhou ZL, Miao ZH, Lin LP, Feng HJ, Tong LJ, Ding J, Li YC.
Abstract : It has long been considered that the free beta hydroxyl group at C14 of triptolide (1) is essential to its potent anticancer activity. In this study, we synthesized novel derivatives of 1 with a hydroxyl group substituted by epoxy groups (4-8) or a five-membered ring (11-13). Compounds (4-8) showed significant in vitro anticancer activity although less potent than 1. Although with an alpha oxygen configuration at the C14 position, (14S)-14,21-epoxytriptolide (4) exhibited the highest potency among all these derivatives, clearly challenging the traditional viewpoint on the necessity of C14beta-hydroxyl group of compound 1. Further studies revealed that while displaying broad spectrum in vitro anticancer activity, compound 4 demonstrated prominent selective in vivo anticancer activity, particularly against human ovarian SK-OV-3 and prostate PC-3 cancers with obviously lower toxicity than 1. Noticeably, compound 4 was also highly effective against multidrug resistant cancer cells. Therefore, our study gives new insights into the structure-activity relationship of 1 and also produces a promising anticancer drug candidate with unique anticancer activities.
|
Cytotoxicity against human PC3 cells after 72 hrs by MTT assay
|
Homo sapiens
|
43.0
nM
|
|
Journal : J. Med. Chem.
Title : Design and synthesis of novel C14-hydroxyl substituted triptolide derivatives as potential selective antitumor agents.
Year : 2009
Volume : 52
Issue : 16
First Page : 5115
Last Page : 5123
Authors : Li Z, Zhou ZL, Miao ZH, Lin LP, Feng HJ, Tong LJ, Ding J, Li YC.
Abstract : It has long been considered that the free beta hydroxyl group at C14 of triptolide (1) is essential to its potent anticancer activity. In this study, we synthesized novel derivatives of 1 with a hydroxyl group substituted by epoxy groups (4-8) or a five-membered ring (11-13). Compounds (4-8) showed significant in vitro anticancer activity although less potent than 1. Although with an alpha oxygen configuration at the C14 position, (14S)-14,21-epoxytriptolide (4) exhibited the highest potency among all these derivatives, clearly challenging the traditional viewpoint on the necessity of C14beta-hydroxyl group of compound 1. Further studies revealed that while displaying broad spectrum in vitro anticancer activity, compound 4 demonstrated prominent selective in vivo anticancer activity, particularly against human ovarian SK-OV-3 and prostate PC-3 cancers with obviously lower toxicity than 1. Noticeably, compound 4 was also highly effective against multidrug resistant cancer cells. Therefore, our study gives new insights into the structure-activity relationship of 1 and also produces a promising anticancer drug candidate with unique anticancer activities.
|
Cytotoxicity against human DU145 cells after 72 hrs by MTT assay
|
Homo sapiens
|
24.0
nM
|
|
Journal : J. Med. Chem.
Title : Design and synthesis of novel C14-hydroxyl substituted triptolide derivatives as potential selective antitumor agents.
Year : 2009
Volume : 52
Issue : 16
First Page : 5115
Last Page : 5123
Authors : Li Z, Zhou ZL, Miao ZH, Lin LP, Feng HJ, Tong LJ, Ding J, Li YC.
Abstract : It has long been considered that the free beta hydroxyl group at C14 of triptolide (1) is essential to its potent anticancer activity. In this study, we synthesized novel derivatives of 1 with a hydroxyl group substituted by epoxy groups (4-8) or a five-membered ring (11-13). Compounds (4-8) showed significant in vitro anticancer activity although less potent than 1. Although with an alpha oxygen configuration at the C14 position, (14S)-14,21-epoxytriptolide (4) exhibited the highest potency among all these derivatives, clearly challenging the traditional viewpoint on the necessity of C14beta-hydroxyl group of compound 1. Further studies revealed that while displaying broad spectrum in vitro anticancer activity, compound 4 demonstrated prominent selective in vivo anticancer activity, particularly against human ovarian SK-OV-3 and prostate PC-3 cancers with obviously lower toxicity than 1. Noticeably, compound 4 was also highly effective against multidrug resistant cancer cells. Therefore, our study gives new insights into the structure-activity relationship of 1 and also produces a promising anticancer drug candidate with unique anticancer activities.
|
Cytotoxicity against human KB cells after 72 hrs by MTT assay
|
Homo sapiens
|
43.0
nM
|
|
Journal : J. Med. Chem.
Title : Design and synthesis of novel C14-hydroxyl substituted triptolide derivatives as potential selective antitumor agents.
Year : 2009
Volume : 52
Issue : 16
First Page : 5115
Last Page : 5123
Authors : Li Z, Zhou ZL, Miao ZH, Lin LP, Feng HJ, Tong LJ, Ding J, Li YC.
Abstract : It has long been considered that the free beta hydroxyl group at C14 of triptolide (1) is essential to its potent anticancer activity. In this study, we synthesized novel derivatives of 1 with a hydroxyl group substituted by epoxy groups (4-8) or a five-membered ring (11-13). Compounds (4-8) showed significant in vitro anticancer activity although less potent than 1. Although with an alpha oxygen configuration at the C14 position, (14S)-14,21-epoxytriptolide (4) exhibited the highest potency among all these derivatives, clearly challenging the traditional viewpoint on the necessity of C14beta-hydroxyl group of compound 1. Further studies revealed that while displaying broad spectrum in vitro anticancer activity, compound 4 demonstrated prominent selective in vivo anticancer activity, particularly against human ovarian SK-OV-3 and prostate PC-3 cancers with obviously lower toxicity than 1. Noticeably, compound 4 was also highly effective against multidrug resistant cancer cells. Therefore, our study gives new insights into the structure-activity relationship of 1 and also produces a promising anticancer drug candidate with unique anticancer activities.
|
Cytotoxicity against human Rh30 cells after 72 hrs by MTT assay
|
Homo sapiens
|
14.0
nM
|
|
Journal : J. Med. Chem.
Title : Design and synthesis of novel C14-hydroxyl substituted triptolide derivatives as potential selective antitumor agents.
Year : 2009
Volume : 52
Issue : 16
First Page : 5115
Last Page : 5123
Authors : Li Z, Zhou ZL, Miao ZH, Lin LP, Feng HJ, Tong LJ, Ding J, Li YC.
Abstract : It has long been considered that the free beta hydroxyl group at C14 of triptolide (1) is essential to its potent anticancer activity. In this study, we synthesized novel derivatives of 1 with a hydroxyl group substituted by epoxy groups (4-8) or a five-membered ring (11-13). Compounds (4-8) showed significant in vitro anticancer activity although less potent than 1. Although with an alpha oxygen configuration at the C14 position, (14S)-14,21-epoxytriptolide (4) exhibited the highest potency among all these derivatives, clearly challenging the traditional viewpoint on the necessity of C14beta-hydroxyl group of compound 1. Further studies revealed that while displaying broad spectrum in vitro anticancer activity, compound 4 demonstrated prominent selective in vivo anticancer activity, particularly against human ovarian SK-OV-3 and prostate PC-3 cancers with obviously lower toxicity than 1. Noticeably, compound 4 was also highly effective against multidrug resistant cancer cells. Therefore, our study gives new insights into the structure-activity relationship of 1 and also produces a promising anticancer drug candidate with unique anticancer activities.
|
Cytotoxicity against human HeLa cells after 72 hrs by MTT assay
|
Homo sapiens
|
47.0
nM
|
|
Journal : J. Med. Chem.
Title : Design and synthesis of novel C14-hydroxyl substituted triptolide derivatives as potential selective antitumor agents.
Year : 2009
Volume : 52
Issue : 16
First Page : 5115
Last Page : 5123
Authors : Li Z, Zhou ZL, Miao ZH, Lin LP, Feng HJ, Tong LJ, Ding J, Li YC.
Abstract : It has long been considered that the free beta hydroxyl group at C14 of triptolide (1) is essential to its potent anticancer activity. In this study, we synthesized novel derivatives of 1 with a hydroxyl group substituted by epoxy groups (4-8) or a five-membered ring (11-13). Compounds (4-8) showed significant in vitro anticancer activity although less potent than 1. Although with an alpha oxygen configuration at the C14 position, (14S)-14,21-epoxytriptolide (4) exhibited the highest potency among all these derivatives, clearly challenging the traditional viewpoint on the necessity of C14beta-hydroxyl group of compound 1. Further studies revealed that while displaying broad spectrum in vitro anticancer activity, compound 4 demonstrated prominent selective in vivo anticancer activity, particularly against human ovarian SK-OV-3 and prostate PC-3 cancers with obviously lower toxicity than 1. Noticeably, compound 4 was also highly effective against multidrug resistant cancer cells. Therefore, our study gives new insights into the structure-activity relationship of 1 and also produces a promising anticancer drug candidate with unique anticancer activities.
|
Cytotoxicity against human U251 cells after 72 hrs by MTT assay
|
Homo sapiens
|
49.0
nM
|
|
Journal : J. Med. Chem.
Title : Design and synthesis of novel C14-hydroxyl substituted triptolide derivatives as potential selective antitumor agents.
Year : 2009
Volume : 52
Issue : 16
First Page : 5115
Last Page : 5123
Authors : Li Z, Zhou ZL, Miao ZH, Lin LP, Feng HJ, Tong LJ, Ding J, Li YC.
Abstract : It has long been considered that the free beta hydroxyl group at C14 of triptolide (1) is essential to its potent anticancer activity. In this study, we synthesized novel derivatives of 1 with a hydroxyl group substituted by epoxy groups (4-8) or a five-membered ring (11-13). Compounds (4-8) showed significant in vitro anticancer activity although less potent than 1. Although with an alpha oxygen configuration at the C14 position, (14S)-14,21-epoxytriptolide (4) exhibited the highest potency among all these derivatives, clearly challenging the traditional viewpoint on the necessity of C14beta-hydroxyl group of compound 1. Further studies revealed that while displaying broad spectrum in vitro anticancer activity, compound 4 demonstrated prominent selective in vivo anticancer activity, particularly against human ovarian SK-OV-3 and prostate PC-3 cancers with obviously lower toxicity than 1. Noticeably, compound 4 was also highly effective against multidrug resistant cancer cells. Therefore, our study gives new insights into the structure-activity relationship of 1 and also produces a promising anticancer drug candidate with unique anticancer activities.
|
Cytotoxicity against human KBM5 cells harboring wild type Bcr-Abl after 72 hrs by MTS assay
|
Homo sapiens
|
10.3
nM
|
|
Journal : Bioorg. Med. Chem.
Title : Design, synthesis, and biological evaluation of novel water-soluble triptolide derivatives: Antineoplastic activity against imatinib-resistant CML cells bearing T315I mutant Bcr-Abl.
Year : 2010
Volume : 18
Issue : 5
First Page : 1806
Last Page : 1815
Authors : Xu F, Shi X, Li S, Cui J, Lu Z, Jin Y, Lin Y, Pang J, Pan J.
Abstract : Imatinib (STI571) is the frontline targeted-therapeutic agent for patients with chronic myelogenous leukemia (CML). However, resistance to imatinib due to point mutations in Bcr-Abl kinase domain is an emerging problem. We recently reported that triptolide (compound 1) could effectively kill CML cells including those harboring T315I mutant Bcr-Abl. In the present study, we designed a series of C-14 triptolide derivatives with C-14-hydroxyl substituted by different amine esters (3-18): 3-6 and 13 (by aliphatic chain amine esters); 7-9, 11, 12 and 15-18 (by alicyclic amine esters with different size), and 10 and 14 (by aralkylamine esters).The compounds were examined for their antineoplastic activity against CML cells (including KBM5-T315I cells) in terms of proliferation inhibition, apoptosis and signal transduction. Nude mouse xenograft model was also used to evaluate the in vivo activity. Compounds 2-9, 11-14, 17 and 18 exhibited a potent inhibitory activity against KBM5 and KBM5-T315I cells. This series of derivatives down-regulated Bcr-Abl mRNA. Compounds 4, 5, 8 and 9 were further examined for their impact on signaling and apoptosis with immunoblotting. Compound 5 was chosen for evaluation in a nude mouse xenograft model. The stereo-hindrance of C-14 group appeared to be responsible for the antitumor effect. The computational small molecule-protein docking analysis illustrated the possible interaction between compound 9 and RNA polymerase II. Our results suggest that this series of derivatives may be promising agents to overcome imatinib-resistance caused by the Bcr-Abl-T315I mutation.
|
Cytotoxicity against imatinib-resistant human KBM5 cells harboring Bcr-Abl T315I mutant after 72 hrs by MTS assay
|
Homo sapiens
|
8.3
nM
|
|
Journal : Bioorg. Med. Chem.
Title : Design, synthesis, and biological evaluation of novel water-soluble triptolide derivatives: Antineoplastic activity against imatinib-resistant CML cells bearing T315I mutant Bcr-Abl.
Year : 2010
Volume : 18
Issue : 5
First Page : 1806
Last Page : 1815
Authors : Xu F, Shi X, Li S, Cui J, Lu Z, Jin Y, Lin Y, Pang J, Pan J.
Abstract : Imatinib (STI571) is the frontline targeted-therapeutic agent for patients with chronic myelogenous leukemia (CML). However, resistance to imatinib due to point mutations in Bcr-Abl kinase domain is an emerging problem. We recently reported that triptolide (compound 1) could effectively kill CML cells including those harboring T315I mutant Bcr-Abl. In the present study, we designed a series of C-14 triptolide derivatives with C-14-hydroxyl substituted by different amine esters (3-18): 3-6 and 13 (by aliphatic chain amine esters); 7-9, 11, 12 and 15-18 (by alicyclic amine esters with different size), and 10 and 14 (by aralkylamine esters).The compounds were examined for their antineoplastic activity against CML cells (including KBM5-T315I cells) in terms of proliferation inhibition, apoptosis and signal transduction. Nude mouse xenograft model was also used to evaluate the in vivo activity. Compounds 2-9, 11-14, 17 and 18 exhibited a potent inhibitory activity against KBM5 and KBM5-T315I cells. This series of derivatives down-regulated Bcr-Abl mRNA. Compounds 4, 5, 8 and 9 were further examined for their impact on signaling and apoptosis with immunoblotting. Compound 5 was chosen for evaluation in a nude mouse xenograft model. The stereo-hindrance of C-14 group appeared to be responsible for the antitumor effect. The computational small molecule-protein docking analysis illustrated the possible interaction between compound 9 and RNA polymerase II. Our results suggest that this series of derivatives may be promising agents to overcome imatinib-resistance caused by the Bcr-Abl-T315I mutation.
|
Cytotoxicity against mouse 32D cells harboring wild type Bcr-Abl after 72 hrs by MTS assay
|
Mus musculus
|
32.0
nM
|
|
Journal : Bioorg. Med. Chem.
Title : Design, synthesis, and biological evaluation of novel water-soluble triptolide derivatives: Antineoplastic activity against imatinib-resistant CML cells bearing T315I mutant Bcr-Abl.
Year : 2010
Volume : 18
Issue : 5
First Page : 1806
Last Page : 1815
Authors : Xu F, Shi X, Li S, Cui J, Lu Z, Jin Y, Lin Y, Pang J, Pan J.
Abstract : Imatinib (STI571) is the frontline targeted-therapeutic agent for patients with chronic myelogenous leukemia (CML). However, resistance to imatinib due to point mutations in Bcr-Abl kinase domain is an emerging problem. We recently reported that triptolide (compound 1) could effectively kill CML cells including those harboring T315I mutant Bcr-Abl. In the present study, we designed a series of C-14 triptolide derivatives with C-14-hydroxyl substituted by different amine esters (3-18): 3-6 and 13 (by aliphatic chain amine esters); 7-9, 11, 12 and 15-18 (by alicyclic amine esters with different size), and 10 and 14 (by aralkylamine esters).The compounds were examined for their antineoplastic activity against CML cells (including KBM5-T315I cells) in terms of proliferation inhibition, apoptosis and signal transduction. Nude mouse xenograft model was also used to evaluate the in vivo activity. Compounds 2-9, 11-14, 17 and 18 exhibited a potent inhibitory activity against KBM5 and KBM5-T315I cells. This series of derivatives down-regulated Bcr-Abl mRNA. Compounds 4, 5, 8 and 9 were further examined for their impact on signaling and apoptosis with immunoblotting. Compound 5 was chosen for evaluation in a nude mouse xenograft model. The stereo-hindrance of C-14 group appeared to be responsible for the antitumor effect. The computational small molecule-protein docking analysis illustrated the possible interaction between compound 9 and RNA polymerase II. Our results suggest that this series of derivatives may be promising agents to overcome imatinib-resistance caused by the Bcr-Abl-T315I mutation.
|
Cytotoxicity against imatinib-resistant mouse 32D cells harboring Bcr-Abl T315I mutant after 72 hrs by MTS assay
|
Mus musculus
|
34.0
nM
|
|
Journal : Bioorg. Med. Chem.
Title : Design, synthesis, and biological evaluation of novel water-soluble triptolide derivatives: Antineoplastic activity against imatinib-resistant CML cells bearing T315I mutant Bcr-Abl.
Year : 2010
Volume : 18
Issue : 5
First Page : 1806
Last Page : 1815
Authors : Xu F, Shi X, Li S, Cui J, Lu Z, Jin Y, Lin Y, Pang J, Pan J.
Abstract : Imatinib (STI571) is the frontline targeted-therapeutic agent for patients with chronic myelogenous leukemia (CML). However, resistance to imatinib due to point mutations in Bcr-Abl kinase domain is an emerging problem. We recently reported that triptolide (compound 1) could effectively kill CML cells including those harboring T315I mutant Bcr-Abl. In the present study, we designed a series of C-14 triptolide derivatives with C-14-hydroxyl substituted by different amine esters (3-18): 3-6 and 13 (by aliphatic chain amine esters); 7-9, 11, 12 and 15-18 (by alicyclic amine esters with different size), and 10 and 14 (by aralkylamine esters).The compounds were examined for their antineoplastic activity against CML cells (including KBM5-T315I cells) in terms of proliferation inhibition, apoptosis and signal transduction. Nude mouse xenograft model was also used to evaluate the in vivo activity. Compounds 2-9, 11-14, 17 and 18 exhibited a potent inhibitory activity against KBM5 and KBM5-T315I cells. This series of derivatives down-regulated Bcr-Abl mRNA. Compounds 4, 5, 8 and 9 were further examined for their impact on signaling and apoptosis with immunoblotting. Compound 5 was chosen for evaluation in a nude mouse xenograft model. The stereo-hindrance of C-14 group appeared to be responsible for the antitumor effect. The computational small molecule-protein docking analysis illustrated the possible interaction between compound 9 and RNA polymerase II. Our results suggest that this series of derivatives may be promising agents to overcome imatinib-resistance caused by the Bcr-Abl-T315I mutation.
|
Antiproliferative activity against human SKOV3 cells after 72 hrs by SRB assay
|
Homo sapiens
|
6.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Synthesis and biological evaluation of novel triptolide analogues for anticancer activity.
Year : 2010
Volume : 20
Issue : 21
First Page : 6217
Last Page : 6221
Authors : Zhou B, Miao Z, Deng G, Ding J, Yang Y, Feng H, Li Y.
Abstract : Three types of novel triptolide analogues with 9,11-olefin (3-5), five-membered unsaturated lactam ring (6-7) or A/B cis ring junction (8-14) were synthesized. Although with 9,11-olefin instead of 9,11-β-epoxide, compound 4a was much more active than the parent natural triptolide (1) with the lowest IC(50) value of 0.05nM for SKOV-3 cells, clearly challenging the traditional viewpoint on the necessity of 9,11-β-epoxide group of triptolide. In addition, structure-activity relationships for three classes of compounds were studied.
|
Antiproliferative activity against human PC3 cells after 72 hrs by SRB assay
|
Homo sapiens
|
20.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Synthesis and biological evaluation of novel triptolide analogues for anticancer activity.
Year : 2010
Volume : 20
Issue : 21
First Page : 6217
Last Page : 6221
Authors : Zhou B, Miao Z, Deng G, Ding J, Yang Y, Feng H, Li Y.
Abstract : Three types of novel triptolide analogues with 9,11-olefin (3-5), five-membered unsaturated lactam ring (6-7) or A/B cis ring junction (8-14) were synthesized. Although with 9,11-olefin instead of 9,11-β-epoxide, compound 4a was much more active than the parent natural triptolide (1) with the lowest IC(50) value of 0.05nM for SKOV-3 cells, clearly challenging the traditional viewpoint on the necessity of 9,11-β-epoxide group of triptolide. In addition, structure-activity relationships for three classes of compounds were studied.
|
PUBCHEM_BIOASSAY: Luminescence Cell-Based Dose Response HTS to Identify Inhibitors of Luciferase Translation or Activity in H4 Neuroglioblastoma Cells. (Class of assay: confirmatory) [Related pubchem assays: 1813 (Primary HTS), 1827 (Project Summary)]
|
None
|
100.0
nM
|
|
Title : PubChem BioAssay data set
|
PUBCHEM_BIOASSAY: Luminescence Cell-Based Dose Response HTS to Identify Inhibitors of 5'UTR Stem-Loop Driven Prion Protein mRNA Translation in H4 Neuroglioblastoma Cells. (Class of assay: confirmatory) [Related pubchem assays: 1827 (Project Summary), 1813 (Primary HTS)]
|
None
|
100.0
nM
|
|
Title : PubChem BioAssay data set
|
PUBCHEM_BIOASSAY: Luminescence Cell-Based Dose Confirmation HTS to Identify Inhibitors of of 5'UTR Stem-Loop Driven Alpha-Synuclein mRNA Translation in H4 Neuroglioblastoma Cells. (Class of assay: confirmatory) [Related pubchem assays: 1827 (Project Summary), 1813 (Primary HTS)]
|
None
|
100.0
nM
|
|
Title : PubChem BioAssay data set
|
Cytotoxicity against human A549 cells
|
Homo sapiens
|
19.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Semisynthesis of triptolide analogues: effect of γ-lactone and C-14 substituents on cytotoxic activities.
Year : 2011
Volume : 21
Issue : 10
First Page : 3046
Last Page : 3049
Authors : Aoyagi Y, Hitotsuyanagi Y, Hasuda T, Fukaya H, Takeya K, Aiyama R, Matsuzaki T, Hashimoto S.
Abstract : Triptolide γ-lactone and C-14 analogues were prepared and evaluated cytotoxity against human lung adenocarcinoma epithelial A549 cells and human colon adenocarcinoma HT-29 cells. γ-Lactone substructure and C-14 substituents affected the biological activities significantly.
|
Cytotoxicity against human HT-29 cells
|
Homo sapiens
|
2.1
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Semisynthesis of triptolide analogues: effect of γ-lactone and C-14 substituents on cytotoxic activities.
Year : 2011
Volume : 21
Issue : 10
First Page : 3046
Last Page : 3049
Authors : Aoyagi Y, Hitotsuyanagi Y, Hasuda T, Fukaya H, Takeya K, Aiyama R, Matsuzaki T, Hashimoto S.
Abstract : Triptolide γ-lactone and C-14 analogues were prepared and evaluated cytotoxity against human lung adenocarcinoma epithelial A549 cells and human colon adenocarcinoma HT-29 cells. γ-Lactone substructure and C-14 substituents affected the biological activities significantly.
|
PUBCHEM_BIOASSAY: Fluorescence Cell-Based Dose Response to Characterize Compounds Cytotoxic to RAS-Dependent BJ-TERT-LT-ST Fibroblast. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID1554, AID1674]
|
None
|
104.0
nM
|
|
Title : PubChem BioAssay data set
|
Antagonist activity at human PAR2 expressed in human A549 cells coexpressing TACR1 assessed as inhibition of substance P-induced IL-8 production by ELISA
|
Homo sapiens
|
23.0
nM
|
|
Journal : J. Med. Chem.
Title : Toward drugs for protease-activated receptor 2 (PAR2).
Year : 2013
Volume : 56
Issue : 19
First Page : 7477
Last Page : 7497
Authors : Yau MK, Liu L, Fairlie DP.
Abstract : PAR2 has a distinctive functional phenotype among an unusual group of GPCRs called protease activated receptors, which self-activate after cleavage of their N-termini by mainly serine proteases. PAR2 is the most highly expressed PAR on certain immune cells, and it is activated by multiple proteases (but not thrombin) in inflammation. PAR2 is expressed on many types of primary human cells and cancer cells. PAR2 knockout mice and PAR2 agonists and antagonists have implicated PAR2 as a promising target in inflammatory conditions; respiratory, gastrointestinal, metabolic, cardiovascular, and neurological dysfunction; and cancers. This article summarizes salient features of PAR2 structure, activation, and function; opportunities for disease intervention via PAR2; pharmacological properties of published or patented PAR2 modulators (small molecule agonists and antagonists, pepducins, antibodies); and some personal perspectives on limitations of assessing their properties and on promising new directions for PAR2 modulation.
|
Antagonist activity at human PAR2 expressed in human A549 cells assessed as inhibition of 2f-LIGRLO-NH2-induced NFkappaB activation by luciferase reporter gene assay
|
Homo sapiens
|
14.0
nM
|
|
Journal : J. Med. Chem.
Title : Toward drugs for protease-activated receptor 2 (PAR2).
Year : 2013
Volume : 56
Issue : 19
First Page : 7477
Last Page : 7497
Authors : Yau MK, Liu L, Fairlie DP.
Abstract : PAR2 has a distinctive functional phenotype among an unusual group of GPCRs called protease activated receptors, which self-activate after cleavage of their N-termini by mainly serine proteases. PAR2 is the most highly expressed PAR on certain immune cells, and it is activated by multiple proteases (but not thrombin) in inflammation. PAR2 is expressed on many types of primary human cells and cancer cells. PAR2 knockout mice and PAR2 agonists and antagonists have implicated PAR2 as a promising target in inflammatory conditions; respiratory, gastrointestinal, metabolic, cardiovascular, and neurological dysfunction; and cancers. This article summarizes salient features of PAR2 structure, activation, and function; opportunities for disease intervention via PAR2; pharmacological properties of published or patented PAR2 modulators (small molecule agonists and antagonists, pepducins, antibodies); and some personal perspectives on limitations of assessing their properties and on promising new directions for PAR2 modulation.
|
Cytotoxicity against human PC3 cells after 72 hrs by sulforhodamine B assay
|
Homo sapiens
|
20.0
nM
|
|
Journal : Eur. J. Med. Chem.
Title : Design, synthesis and anticancer activity evaluation of novel C14 heterocycle substituted epi-triptolide.
Year : 2014
Volume : 73
First Page : 46
Last Page : 55
Authors : Xu H, Tang H, Feng H, Li Y.
Abstract : Two series of novel C14 heterocycle substituted epi-triptolide derivatives as potential anticancer agents were synthesized and tested for their cytotoxicity against SKOV-3 and PC-3 tumor cell lines. The introduction of C14β-aryl heterocycle aminomethyl substituent to the leading compound was found to be an effective modification method to retain the potent anticancer activity. Meanwhile, the series of epi-triptolide derivatives (21-40) with C14α-hydroxyl group, still retained the natural product's cytotoxicity. This is apparently challenges the classical structure-activity relationship of triptolide that considers the C14β-hydroxyl group to be essential for its anticancer activity.
|
Cytotoxicity against human SKOV3 cells after 72 hrs by sulforhodamine B assay
|
Homo sapiens
|
6.0
nM
|
|
Journal : Eur. J. Med. Chem.
Title : Design, synthesis and anticancer activity evaluation of novel C14 heterocycle substituted epi-triptolide.
Year : 2014
Volume : 73
First Page : 46
Last Page : 55
Authors : Xu H, Tang H, Feng H, Li Y.
Abstract : Two series of novel C14 heterocycle substituted epi-triptolide derivatives as potential anticancer agents were synthesized and tested for their cytotoxicity against SKOV-3 and PC-3 tumor cell lines. The introduction of C14β-aryl heterocycle aminomethyl substituent to the leading compound was found to be an effective modification method to retain the potent anticancer activity. Meanwhile, the series of epi-triptolide derivatives (21-40) with C14α-hydroxyl group, still retained the natural product's cytotoxicity. This is apparently challenges the classical structure-activity relationship of triptolide that considers the C14β-hydroxyl group to be essential for its anticancer activity.
|
Cytotoxicity against human U251 cells assessed as inhibition of cell proliferation by sulforhodamine B assay
|
Homo sapiens
|
33.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Semisynthesis of triptolide analogues: effect of B-ring substituents on cytotoxic activities.
Year : 2014
Volume : 24
Issue : 24
First Page : 5671
Last Page : 5674
Authors : Xu H, Chen Y, Tang H, Feng H, Li Y.
Abstract : A series of B-ring modified analogues of triptolide were synthesized and tested for their cytotoxicity against two human tumor cell lines (U251 and PC-3). From the current investigation, the structure-cytotoxic activity relationships of these analogues suggested that the introduction of hydroxyl, epoxide, halogen or olefinic groups on C5 and/or C6 could still retain the cytotoxicity, albeit a little less potency, and the C7,C8-β-epoxide group of triptolide was essential to its potent cytotoxic activity.
|
Cytotoxicity against human PC3 cells assessed as inhibition of cell proliferation by sulforhodamine B assay
|
Homo sapiens
|
20.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Semisynthesis of triptolide analogues: effect of B-ring substituents on cytotoxic activities.
Year : 2014
Volume : 24
Issue : 24
First Page : 5671
Last Page : 5674
Authors : Xu H, Chen Y, Tang H, Feng H, Li Y.
Abstract : A series of B-ring modified analogues of triptolide were synthesized and tested for their cytotoxicity against two human tumor cell lines (U251 and PC-3). From the current investigation, the structure-cytotoxic activity relationships of these analogues suggested that the introduction of hydroxyl, epoxide, halogen or olefinic groups on C5 and/or C6 could still retain the cytotoxicity, albeit a little less potency, and the C7,C8-β-epoxide group of triptolide was essential to its potent cytotoxic activity.
|
Cytotoxic activity against human A549 cells assessed as reduction in cell viability after 72 hrs by SRB assay
|
Homo sapiens
|
17.5
nM
|
|
Journal : Bioorg Med Chem Lett
Title : Identification of a diverse synthetic abietane diterpenoid library for anticancer activity.
Year : 2017
Volume : 27
Issue : 3
First Page : 505
Last Page : 510
Authors : Xu H, Liu L, Fan X, Zhang G, Li Y, Jiang B.
Abstract : A diverse natural-product-like synthetic abietane diterpenoid library contains about 56 compounds were obtained, and evaluated for their potential in vitro cytotoxic or antitumor activity against A549, PC-3 and SKOV-3 tumor cell lines by SRB assay. Treatment of A549 cells with the most potent compound ketone 19 showed induction of apoptosis, as revealed by JC-1 mitochondrial membrane potential staining, TUNNEL assay, western blotting analysis and flow cytometry assay.
|
Cytotoxic activity against human SKOV3 cells assessed as reduction in cell viability after 72 hrs by SRB assay
|
Homo sapiens
|
7.2
nM
|
|
Journal : Bioorg Med Chem Lett
Title : Identification of a diverse synthetic abietane diterpenoid library for anticancer activity.
Year : 2017
Volume : 27
Issue : 3
First Page : 505
Last Page : 510
Authors : Xu H, Liu L, Fan X, Zhang G, Li Y, Jiang B.
Abstract : A diverse natural-product-like synthetic abietane diterpenoid library contains about 56 compounds were obtained, and evaluated for their potential in vitro cytotoxic or antitumor activity against A549, PC-3 and SKOV-3 tumor cell lines by SRB assay. Treatment of A549 cells with the most potent compound ketone 19 showed induction of apoptosis, as revealed by JC-1 mitochondrial membrane potential staining, TUNNEL assay, western blotting analysis and flow cytometry assay.
|
Cytotoxic activity against human PC3 cells assessed as reduction in cell viability after 72 hrs by SRB assay
|
Homo sapiens
|
18.3
nM
|
|
Journal : Bioorg Med Chem Lett
Title : Identification of a diverse synthetic abietane diterpenoid library for anticancer activity.
Year : 2017
Volume : 27
Issue : 3
First Page : 505
Last Page : 510
Authors : Xu H, Liu L, Fan X, Zhang G, Li Y, Jiang B.
Abstract : A diverse natural-product-like synthetic abietane diterpenoid library contains about 56 compounds were obtained, and evaluated for their potential in vitro cytotoxic or antitumor activity against A549, PC-3 and SKOV-3 tumor cell lines by SRB assay. Treatment of A549 cells with the most potent compound ketone 19 showed induction of apoptosis, as revealed by JC-1 mitochondrial membrane potential staining, TUNNEL assay, western blotting analysis and flow cytometry assay.
|
Growth inhibition of human A549 cells
|
Homo sapiens
|
30.0
nM
|
|
Journal : Eur J Med Chem
Title : From bench (laboratory) to bed (hospital/home): How to explore effective natural and synthetic PAK1-blockers/longevity-promoters for cancer therapy.
Year : 2017
Volume : 142
First Page : 229
Last Page : 243
Authors : Maruta H, Ahn MR.
Abstract : PAK family kinases are RAC/CDC42-activated kinases that were first found in a soil amoeba 4 decades ago, and 2 decades later, were discovered in mammals as well. Since then at least 6 members of this family have been identified in mammals. One of them called PAK1 has been best studied so far, mainly because it is essential not only for malignant cell growth and metastasis, but also for many other diseases/disorders such as diabetes (type 2), AD (Alzheimer's disease), hypertension, and a variety of inflammatory or infectious diseases, which definitely shorten our lifespan. Moreover, PAK1-deficient mutant of C. elegans lives longer than the wild-type by 60%, clearly indicating that PAK1 is not only an oncogenic but also ageing kinase. Thus, in theory, both anti-oncogenic and longevity-promoting activities are among the "intrinsic" properties or criteria of "clinically useful" PAK1-blockers. There are a variety of PAK1-blocking natural products such as propolis and curcumin which indeed extend the healthy lifespan of small animals such as C. elegans by inducing the autophagy. Recently, we managed to synthesize a series of potent water-soluble and highly cell-permeable triazolyl esters of COOH-bearing PAK1-blockers such as Ketorolac, ARC (artepillin C) and CA (caffeic acid) via "Click Chemistry" that boosts their anti-cancer activity over 500-fold, mainly by increasing their cell-permeability, and one of them called 15K indeed extends the lifespan of C. elegans. In this mini-review we shall discuss both synthetic and natural PAK1-blockers, some of which would be potentially useful for cancer therapy with least side effect (rather promoting the longevity as well).
|
Antibacterial activity against Staphylococcus aureus MRSA ATCC 43300 (CO-ADD:GP_020); MIC in CAMBH media, using NBS plates, by OD(600)
|
Staphylococcus aureus subsp. aureus
|
14.16
%
|
|
|
Antibacterial activity against Escherichia coli ATCC 25922 (CO-ADD:GN_001); MIC in CAMBH media using NBS plates, by OD(600)
|
Escherichia coli
|
-9.75
%
|
|
|
Antibacterial activity against Klebsiella pneumoniae MDR ATCC 70063 (CO-ADD:GN_003); MIC in CAMBH media using NBS plates, by OD(600)
|
Klebsiella pneumoniae
|
7.24
%
|
|
|
Antibacterial activity against Pseudomonas aeruginosa ATCC 27853 (CO-ADD:GN_042); MIC in CAMBH media using NBS plates, by OD(600)
|
Pseudomonas aeruginosa
|
24.45
%
|
|
|
Antibacterial activity against Acinetobacter baumannii ATCC 19606 (CO-ADD:GN_034); MIC in CAMBH media using NBS plates, by OD600
|
Acinetobacter baumannii
|
17.86
%
|
|
|
Antifungal activity against Candida albicans ATCC 90028 (CO-ADD:FG_001); MIC in YNB media using NBS plates, by OD630
|
Candida albicans
|
1.65
%
|
|
|
Antifungal activity against Cryptococcus neoformans H99 ATCC 208821 (CO-ADD:FG_002); MIC in YNB media using NBS plates, by Resazurin OD(600-570)
|
Cryptococcus neoformans
|
-8.43
%
|
|
|
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of Caco-2 cells at 10 uM after 48 hours by high content imaging
|
Homo sapiens
|
90.67
%
|
|
Title : Identification of inhibitors of SARS-CoV-2 in-vitro cellular toxicity in human (Caco-2) cells using a large scale drug repurposing collection
Year : 2020
Authors : Bernhard Ellinger, Denisa Bojkova, Andrea Zaliani, Jindrich Cinatl, Carsten Claussen, Sandra Westhaus, Jeanette Reinshagen, Maria Kuzikov, Markus Wolf, Gerd Geisslinger, Philip Gribbon, Sandra Ciesek
Abstract : To identify possible candidates for progression towards clinical studies against SARS-CoV-2, we screened a well-defined collection of 5632 compounds including 3488 compounds which have undergone clinical investigations (marketed drugs, phases 1 -3, and withdrawn) across 600 indications. Compounds were screened for their inhibition of viral induced cytotoxicity using the human epithelial colorectal adenocarcinoma cell line Caco-2 and a SARS-CoV-2 isolate. The primary screen of 5632 compounds gave 271 hits. A total of 64 compounds with IC50 <20 µM were identified, including 19 compounds with IC50 < 1 µM. Of this confirmed hit population, 90% have not yet been previously reported as active against SARS-CoV-2 in-vitro cell assays. Some 37 of the actives are launched drugs, 19 are in phases 1-3 and 10 pre-clinical. Several inhibitors were associated with modulation of host pathways including kinase signaling P53 activation, ubiquitin pathways and PDE activity modulation, with long chain acyl transferases were effective viral inhibitors.
|
Cytotoxicity against human HCT116 cells assessed as decrease in cell viability
|
Homo sapiens
|
4.7
nM
|
|
Journal : Eur J Med Chem
Title : Triptolide: Medicinal chemistry, chemical biology and clinical progress.
Year : 2019
Volume : 176
First Page : 378
Last Page : 392
Authors : Hou W, Liu B, Xu H.
Abstract : In the past decades, triptolide has attracted considerable interests in the organic and medicinal chemistry society owing to its intriguing structure features and promising multiple pharmacological activities. However, its limited water solubility and oral bioavailability, imprecise mechanism of action and sever toxicity, scares from nature and difficulty in the synthesis have greatly hindered its clinical potential. Hence, to circumvent such problems, a lot of elegant total synthesis have been developed. With the advancement of the total synthesis, various triptolide derivatives have been synthesized and tested in the search for more drug-like derivatives for potential anticancer agents, anti-inflammatory agents, immunosuppressive agents and anti-Alzheimer's agents, etc. Meanwhile, through designing and synthesizing of various of bioactive probes, some molecular targets that are responsible for the multiple pharmacology activities as well as toxicity of triptolide have been identified. It is no doubt will help the future development of new drug-like triptolide derivatives. In order to gain a comprehensive and deep understanding of the area and provides suggestions for triptolide's further studies, i) the medicinal chemistry advancement, ii) bioactive probes-based cellular target identification and iii) clinical progress of triptolide derivatives are reviewed in this article.
|
Cytotoxicity against human HeLa cells assessed as decrease in cell viability
|
Homo sapiens
|
87.0
nM
|
|
Journal : Eur J Med Chem
Title : Triptolide: Medicinal chemistry, chemical biology and clinical progress.
Year : 2019
Volume : 176
First Page : 378
Last Page : 392
Authors : Hou W, Liu B, Xu H.
Abstract : In the past decades, triptolide has attracted considerable interests in the organic and medicinal chemistry society owing to its intriguing structure features and promising multiple pharmacological activities. However, its limited water solubility and oral bioavailability, imprecise mechanism of action and sever toxicity, scares from nature and difficulty in the synthesis have greatly hindered its clinical potential. Hence, to circumvent such problems, a lot of elegant total synthesis have been developed. With the advancement of the total synthesis, various triptolide derivatives have been synthesized and tested in the search for more drug-like derivatives for potential anticancer agents, anti-inflammatory agents, immunosuppressive agents and anti-Alzheimer's agents, etc. Meanwhile, through designing and synthesizing of various of bioactive probes, some molecular targets that are responsible for the multiple pharmacology activities as well as toxicity of triptolide have been identified. It is no doubt will help the future development of new drug-like triptolide derivatives. In order to gain a comprehensive and deep understanding of the area and provides suggestions for triptolide's further studies, i) the medicinal chemistry advancement, ii) bioactive probes-based cellular target identification and iii) clinical progress of triptolide derivatives are reviewed in this article.
|
Cytotoxicity against human Jurkat cells assessed as decrease in cell viability
|
Homo sapiens
|
140.0
nM
|
|
Journal : Eur J Med Chem
Title : Triptolide: Medicinal chemistry, chemical biology and clinical progress.
Year : 2019
Volume : 176
First Page : 378
Last Page : 392
Authors : Hou W, Liu B, Xu H.
Abstract : In the past decades, triptolide has attracted considerable interests in the organic and medicinal chemistry society owing to its intriguing structure features and promising multiple pharmacological activities. However, its limited water solubility and oral bioavailability, imprecise mechanism of action and sever toxicity, scares from nature and difficulty in the synthesis have greatly hindered its clinical potential. Hence, to circumvent such problems, a lot of elegant total synthesis have been developed. With the advancement of the total synthesis, various triptolide derivatives have been synthesized and tested in the search for more drug-like derivatives for potential anticancer agents, anti-inflammatory agents, immunosuppressive agents and anti-Alzheimer's agents, etc. Meanwhile, through designing and synthesizing of various of bioactive probes, some molecular targets that are responsible for the multiple pharmacology activities as well as toxicity of triptolide have been identified. It is no doubt will help the future development of new drug-like triptolide derivatives. In order to gain a comprehensive and deep understanding of the area and provides suggestions for triptolide's further studies, i) the medicinal chemistry advancement, ii) bioactive probes-based cellular target identification and iii) clinical progress of triptolide derivatives are reviewed in this article.
|
Cytotoxicity against mouse NIH/3T3 cells assessed as decrease in cell viability
|
Mus musculus
|
50.0
nM
|
|
Journal : Eur J Med Chem
Title : Triptolide: Medicinal chemistry, chemical biology and clinical progress.
Year : 2019
Volume : 176
First Page : 378
Last Page : 392
Authors : Hou W, Liu B, Xu H.
Abstract : In the past decades, triptolide has attracted considerable interests in the organic and medicinal chemistry society owing to its intriguing structure features and promising multiple pharmacological activities. However, its limited water solubility and oral bioavailability, imprecise mechanism of action and sever toxicity, scares from nature and difficulty in the synthesis have greatly hindered its clinical potential. Hence, to circumvent such problems, a lot of elegant total synthesis have been developed. With the advancement of the total synthesis, various triptolide derivatives have been synthesized and tested in the search for more drug-like derivatives for potential anticancer agents, anti-inflammatory agents, immunosuppressive agents and anti-Alzheimer's agents, etc. Meanwhile, through designing and synthesizing of various of bioactive probes, some molecular targets that are responsible for the multiple pharmacology activities as well as toxicity of triptolide have been identified. It is no doubt will help the future development of new drug-like triptolide derivatives. In order to gain a comprehensive and deep understanding of the area and provides suggestions for triptolide's further studies, i) the medicinal chemistry advancement, ii) bioactive probes-based cellular target identification and iii) clinical progress of triptolide derivatives are reviewed in this article.
|
Cytotoxicity against human Bre01 cells assessed as decrease in cell viability
|
Homo sapiens
|
0.04
ug.mL-1
|
|
Journal : Eur J Med Chem
Title : Triptolide: Medicinal chemistry, chemical biology and clinical progress.
Year : 2019
Volume : 176
First Page : 378
Last Page : 392
Authors : Hou W, Liu B, Xu H.
Abstract : In the past decades, triptolide has attracted considerable interests in the organic and medicinal chemistry society owing to its intriguing structure features and promising multiple pharmacological activities. However, its limited water solubility and oral bioavailability, imprecise mechanism of action and sever toxicity, scares from nature and difficulty in the synthesis have greatly hindered its clinical potential. Hence, to circumvent such problems, a lot of elegant total synthesis have been developed. With the advancement of the total synthesis, various triptolide derivatives have been synthesized and tested in the search for more drug-like derivatives for potential anticancer agents, anti-inflammatory agents, immunosuppressive agents and anti-Alzheimer's agents, etc. Meanwhile, through designing and synthesizing of various of bioactive probes, some molecular targets that are responsible for the multiple pharmacology activities as well as toxicity of triptolide have been identified. It is no doubt will help the future development of new drug-like triptolide derivatives. In order to gain a comprehensive and deep understanding of the area and provides suggestions for triptolide's further studies, i) the medicinal chemistry advancement, ii) bioactive probes-based cellular target identification and iii) clinical progress of triptolide derivatives are reviewed in this article.
|
Cytotoxicity against human Col-06 cells assessed as decrease in cell viability
|
Homo sapiens
|
0.02
ug.mL-1
|
|
Journal : Eur J Med Chem
Title : Triptolide: Medicinal chemistry, chemical biology and clinical progress.
Year : 2019
Volume : 176
First Page : 378
Last Page : 392
Authors : Hou W, Liu B, Xu H.
Abstract : In the past decades, triptolide has attracted considerable interests in the organic and medicinal chemistry society owing to its intriguing structure features and promising multiple pharmacological activities. However, its limited water solubility and oral bioavailability, imprecise mechanism of action and sever toxicity, scares from nature and difficulty in the synthesis have greatly hindered its clinical potential. Hence, to circumvent such problems, a lot of elegant total synthesis have been developed. With the advancement of the total synthesis, various triptolide derivatives have been synthesized and tested in the search for more drug-like derivatives for potential anticancer agents, anti-inflammatory agents, immunosuppressive agents and anti-Alzheimer's agents, etc. Meanwhile, through designing and synthesizing of various of bioactive probes, some molecular targets that are responsible for the multiple pharmacology activities as well as toxicity of triptolide have been identified. It is no doubt will help the future development of new drug-like triptolide derivatives. In order to gain a comprehensive and deep understanding of the area and provides suggestions for triptolide's further studies, i) the medicinal chemistry advancement, ii) bioactive probes-based cellular target identification and iii) clinical progress of triptolide derivatives are reviewed in this article.
|
Cytotoxicity against human SK-MEL-8 cells assessed as decrease in cell viability
|
Homo sapiens
|
0.02
ug.mL-1
|
|
Journal : Eur J Med Chem
Title : Triptolide: Medicinal chemistry, chemical biology and clinical progress.
Year : 2019
Volume : 176
First Page : 378
Last Page : 392
Authors : Hou W, Liu B, Xu H.
Abstract : In the past decades, triptolide has attracted considerable interests in the organic and medicinal chemistry society owing to its intriguing structure features and promising multiple pharmacological activities. However, its limited water solubility and oral bioavailability, imprecise mechanism of action and sever toxicity, scares from nature and difficulty in the synthesis have greatly hindered its clinical potential. Hence, to circumvent such problems, a lot of elegant total synthesis have been developed. With the advancement of the total synthesis, various triptolide derivatives have been synthesized and tested in the search for more drug-like derivatives for potential anticancer agents, anti-inflammatory agents, immunosuppressive agents and anti-Alzheimer's agents, etc. Meanwhile, through designing and synthesizing of various of bioactive probes, some molecular targets that are responsible for the multiple pharmacology activities as well as toxicity of triptolide have been identified. It is no doubt will help the future development of new drug-like triptolide derivatives. In order to gain a comprehensive and deep understanding of the area and provides suggestions for triptolide's further studies, i) the medicinal chemistry advancement, ii) bioactive probes-based cellular target identification and iii) clinical progress of triptolide derivatives are reviewed in this article.
|
Cytotoxicity against human OVCAR1 cells assessed as decrease in cell viability
|
Homo sapiens
|
0.006
ug.mL-1
|
|
Journal : Eur J Med Chem
Title : Triptolide: Medicinal chemistry, chemical biology and clinical progress.
Year : 2019
Volume : 176
First Page : 378
Last Page : 392
Authors : Hou W, Liu B, Xu H.
Abstract : In the past decades, triptolide has attracted considerable interests in the organic and medicinal chemistry society owing to its intriguing structure features and promising multiple pharmacological activities. However, its limited water solubility and oral bioavailability, imprecise mechanism of action and sever toxicity, scares from nature and difficulty in the synthesis have greatly hindered its clinical potential. Hence, to circumvent such problems, a lot of elegant total synthesis have been developed. With the advancement of the total synthesis, various triptolide derivatives have been synthesized and tested in the search for more drug-like derivatives for potential anticancer agents, anti-inflammatory agents, immunosuppressive agents and anti-Alzheimer's agents, etc. Meanwhile, through designing and synthesizing of various of bioactive probes, some molecular targets that are responsible for the multiple pharmacology activities as well as toxicity of triptolide have been identified. It is no doubt will help the future development of new drug-like triptolide derivatives. In order to gain a comprehensive and deep understanding of the area and provides suggestions for triptolide's further studies, i) the medicinal chemistry advancement, ii) bioactive probes-based cellular target identification and iii) clinical progress of triptolide derivatives are reviewed in this article.
|
Cytotoxicity against human Re-01 cells assessed as decrease in cell viability
|
Homo sapiens
|
0.03
ug.mL-1
|
|
Journal : Eur J Med Chem
Title : Triptolide: Medicinal chemistry, chemical biology and clinical progress.
Year : 2019
Volume : 176
First Page : 378
Last Page : 392
Authors : Hou W, Liu B, Xu H.
Abstract : In the past decades, triptolide has attracted considerable interests in the organic and medicinal chemistry society owing to its intriguing structure features and promising multiple pharmacological activities. However, its limited water solubility and oral bioavailability, imprecise mechanism of action and sever toxicity, scares from nature and difficulty in the synthesis have greatly hindered its clinical potential. Hence, to circumvent such problems, a lot of elegant total synthesis have been developed. With the advancement of the total synthesis, various triptolide derivatives have been synthesized and tested in the search for more drug-like derivatives for potential anticancer agents, anti-inflammatory agents, immunosuppressive agents and anti-Alzheimer's agents, etc. Meanwhile, through designing and synthesizing of various of bioactive probes, some molecular targets that are responsible for the multiple pharmacology activities as well as toxicity of triptolide have been identified. It is no doubt will help the future development of new drug-like triptolide derivatives. In order to gain a comprehensive and deep understanding of the area and provides suggestions for triptolide's further studies, i) the medicinal chemistry advancement, ii) bioactive probes-based cellular target identification and iii) clinical progress of triptolide derivatives are reviewed in this article.
|
Cytotoxicity against human HepG2 cells after 48 hrs by XTT assay
|
Homo sapiens
|
43.3
nM
|
|
Journal : ACS Med Chem Lett
Title : NQO1-Selective Activated Prodrug of Triptolide: Synthesis and Antihepatocellular Carcinoma Activity Evaluation.
Year : 2018
Volume : 9
Issue : 12
First Page : 1253
Last Page : 1257
Authors : Liu M, Song W, Du X, Su J, Dong K, Chen Y, Peng Z.
Abstract : Hepatocellular carcinoma (HCC) is the leading cause of death in patients with cirrhosis. Due to its poor response to conventional chemotherapy drugs, the prognosis for its survival is the worst. NAD(P)H:quinone oxidoreductase 1 (NQO1) is an attractive anticancer target due to its overexpression in HCC. Although triptolide (TP) possesses potent antitumor activity, its clinical practice is greatly limited due to its general toxicities and narrow therapeutic window. Herein, we develop an NQO1-selective activated TP analog, named CX-23, which exhibited antiproliferation of HepG2 over normal hepatocytes in vitro. In vivo study shows that CX-23 can not only prevent the hepatocellular carcinoma progression but also migrate the liver and kidney toxicity. These findings indicate that NQO1 may serve as a targeted delivery system to release an antitumor reagent and that CX-23 may be a promising lead for developing targeted antihepatocellular carcinoma drugs.
|
Cytotoxicity against primary hepatocytes (unknown origin) after 48 hrs by XTT assay
|
Not specified
|
37.7
nM
|
|
Journal : ACS Med Chem Lett
Title : NQO1-Selective Activated Prodrug of Triptolide: Synthesis and Antihepatocellular Carcinoma Activity Evaluation.
Year : 2018
Volume : 9
Issue : 12
First Page : 1253
Last Page : 1257
Authors : Liu M, Song W, Du X, Su J, Dong K, Chen Y, Peng Z.
Abstract : Hepatocellular carcinoma (HCC) is the leading cause of death in patients with cirrhosis. Due to its poor response to conventional chemotherapy drugs, the prognosis for its survival is the worst. NAD(P)H:quinone oxidoreductase 1 (NQO1) is an attractive anticancer target due to its overexpression in HCC. Although triptolide (TP) possesses potent antitumor activity, its clinical practice is greatly limited due to its general toxicities and narrow therapeutic window. Herein, we develop an NQO1-selective activated TP analog, named CX-23, which exhibited antiproliferation of HepG2 over normal hepatocytes in vitro. In vivo study shows that CX-23 can not only prevent the hepatocellular carcinoma progression but also migrate the liver and kidney toxicity. These findings indicate that NQO1 may serve as a targeted delivery system to release an antitumor reagent and that CX-23 may be a promising lead for developing targeted antihepatocellular carcinoma drugs.
|
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate
|
Severe acute respiratory syndrome coronavirus 2
|
6.6
%
|
|
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate
|
Severe acute respiratory syndrome coronavirus 2
|
-6.471
%
|
|
Title : Identification of inhibitors of SARS-Cov2 M-Pro enzymatic activity using a small molecule repurposing screen
Year : 2020
Authors : Maria Kuzikov, Elisa Costanzi, Jeanette Reinshagen, Francesca Esposito, Laura Vangeel, Markus Wolf, Bernhard Ellinger, Carsten Claussen, Gerd Geisslinger, Angela Corona, Daniela Iaconis, Carmine Talarico, Candida Manelfi, Rolando Cannalire, Giulia Rossetti, Jonas Gossen, Simone Albani, Francesco Musiani, Katja Herzog, Yang Ye, Barbara Giabbai, Nicola Demitri, Dirk Jochmans, Steven De Jonghe, Jasper Rymenants, Vincenzo Summa, Enzo Tramontano, Andrea R. Beccari, Pieter Leyssen, Paola Storici, Johan Neyts, Philip Gribbon, and Andrea Zaliani
Abstract : Compound repurposing is an important strategy being pursued in the identification of effective treatment against the SARS-CoV-2 infection and COVID-19 disease. In this regard, SARS-CoV-2 main protease (M-Pro), also termed 3CL-Pro, is an attractive drug target as it plays a central role in viral replication by processing the viral polyprotein into 11 non-structural proteins. We report the results of a screening campaign involving ca 8.7 K compounds containing marketed drugs, clinical and preclinical candidates, and chemicals regarded as safe in humans. We confirmed previously reported inhibitors of 3CL-Pro, but we have also identified 68 compounds with IC50 lower than 1 uM and 127 compounds with IC50 lower than 5 uM. Profiling showed 67% of confirmed hits were selective (> 5 fold) against other Cys- and Ser- proteases (Chymotrypsin and Cathepsin-L) and MERS 3CL-Pro. Selected compounds were also analysed in their binding characteristics.
|
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging
|
Chlorocebus sabaeus
|
2.1
%
|
|
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging
|
Chlorocebus sabaeus
|
1.32
%
|
|
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging
|
Chlorocebus sabaeus
|
1.32
%
|
|
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging
|
Chlorocebus sabaeus
|
2.1
%
|
|
Title : Cytopathic SARS-Cov2 screening on VERO-E6 cells in a large repurposing effort
Year : 2020
Authors : Andrea Zaliani, Laura Vangeel, Jeanette Reinshagen, Daniela Iaconis, Maria Kuzikov, Oliver Keminer, Markus Wolf, Bernhard Ellinger, Francesca Esposito, Angela Corona, Enzo Tramontano, Candida Manelfi, Katja Herzog, Dirk Jochmans, Steven De Jonghe, Winston Chiu, Thibault Francken, Joost Schepers, Caroline Collard, Kayvan Abbasi, Carsten Claussen , Vincenzo Summa, Andrea R. Beccari, Johan Neyts, Philip Gribbon and Pieter Leyssen
Abstract : Worldwide, there are intensive efforts to identify repurposed drugs as potential therapies against SARS-CoV-2 infection and the associated COVID-19 disease. To date, the anti-inflammatory drug dexamethasone and (to a lesser extent) the RNA-polymerase inhibitor remdesivir have been shown to be effective in reducing mortality and patient time to recovery, respectively, in patients. Here, we report the results of a phenotypic screening campaign within an EU-funded project (H2020-EXSCALATE4COV) aimed at extending the repertoire of anti-COVID therapeutics through repurposing of available compounds and highlighting compounds with new mechanisms of action against viral infection. We screened 8702 molecules from different repurposing libraries, to reveal 110 compounds with an anti-cytopathic IC50 < 20 µM. From this group, 18 with a safety index greater than 2 are also marketed drugs, making them suitable for further study as potential therapies against COVID-19. Our result supports the idea that a systematic approach to repurposing is a valid strategy to accelerate the necessary drug discovery process.
|
Antiproliferative activity against human HCT-116 cells assessed as reduction in cell growth incubated for 96 hrs by MTT assay
|
Homo sapiens
|
3.0
nM
|
|
Journal : Eur J Med Chem
Title : Novel nitric oxide-releasing derivatives of triptolide as antitumor and anti-inflammatory agents: Design, synthesis, biological evaluation, and nitric oxide release studies.
Year : 2020
Volume : 190
First Page : 112079
Last Page : 112079
Authors : Zang Y,Lai F,Fu J,Li C,Ma J,Chen C,Liu K,Zhang T,Chen X,Zhang D
Abstract : A series of novel triptolide/furoxans hybrids were designed and synthesized as analogues of triptolide, which is a naturally derived compound isolated from the thunder god vine (Tripterygium wilfordii Hook. F). Some of these synthesized compounds exhibited antiproliferative activities in the nanomolar range. Among them, compound 33 exhibited both good antiproliferative activity and NO-releasing ability and the acute toxicity of compound 33 decreased more than 160 times (LD = 160.9 mg/kg) than triptolide. Moreover, compound 33 significantly inhibited the growth of melanoma at a low dose (0.3 mg/kg) and showed strong anti-inflammatory activity in vitro and in vivo. These results indicate that compound 33 could be a promising candidate for further study.
|
Antiproliferative activity against human HepG2 cells assessed as reduction in cell growth incubated for 96 hrs by MTT assay
|
Homo sapiens
|
14.0
nM
|
|
Journal : Eur J Med Chem
Title : Novel nitric oxide-releasing derivatives of triptolide as antitumor and anti-inflammatory agents: Design, synthesis, biological evaluation, and nitric oxide release studies.
Year : 2020
Volume : 190
First Page : 112079
Last Page : 112079
Authors : Zang Y,Lai F,Fu J,Li C,Ma J,Chen C,Liu K,Zhang T,Chen X,Zhang D
Abstract : A series of novel triptolide/furoxans hybrids were designed and synthesized as analogues of triptolide, which is a naturally derived compound isolated from the thunder god vine (Tripterygium wilfordii Hook. F). Some of these synthesized compounds exhibited antiproliferative activities in the nanomolar range. Among them, compound 33 exhibited both good antiproliferative activity and NO-releasing ability and the acute toxicity of compound 33 decreased more than 160 times (LD = 160.9 mg/kg) than triptolide. Moreover, compound 33 significantly inhibited the growth of melanoma at a low dose (0.3 mg/kg) and showed strong anti-inflammatory activity in vitro and in vivo. These results indicate that compound 33 could be a promising candidate for further study.
|
Antiproliferative activity against human BGC-823 cells assessed as reduction in cell growth incubated for 96 hrs by MTT assay
|
Homo sapiens
|
2.0
nM
|
|
Journal : Eur J Med Chem
Title : Novel nitric oxide-releasing derivatives of triptolide as antitumor and anti-inflammatory agents: Design, synthesis, biological evaluation, and nitric oxide release studies.
Year : 2020
Volume : 190
First Page : 112079
Last Page : 112079
Authors : Zang Y,Lai F,Fu J,Li C,Ma J,Chen C,Liu K,Zhang T,Chen X,Zhang D
Abstract : A series of novel triptolide/furoxans hybrids were designed and synthesized as analogues of triptolide, which is a naturally derived compound isolated from the thunder god vine (Tripterygium wilfordii Hook. F). Some of these synthesized compounds exhibited antiproliferative activities in the nanomolar range. Among them, compound 33 exhibited both good antiproliferative activity and NO-releasing ability and the acute toxicity of compound 33 decreased more than 160 times (LD = 160.9 mg/kg) than triptolide. Moreover, compound 33 significantly inhibited the growth of melanoma at a low dose (0.3 mg/kg) and showed strong anti-inflammatory activity in vitro and in vivo. These results indicate that compound 33 could be a promising candidate for further study.
|
Antiproliferative activity against human NCI-H1650 cells assessed as reduction in cell growth incubated for 96 hrs by MTT assay
|
Homo sapiens
|
15.0
nM
|
|
Journal : Eur J Med Chem
Title : Novel nitric oxide-releasing derivatives of triptolide as antitumor and anti-inflammatory agents: Design, synthesis, biological evaluation, and nitric oxide release studies.
Year : 2020
Volume : 190
First Page : 112079
Last Page : 112079
Authors : Zang Y,Lai F,Fu J,Li C,Ma J,Chen C,Liu K,Zhang T,Chen X,Zhang D
Abstract : A series of novel triptolide/furoxans hybrids were designed and synthesized as analogues of triptolide, which is a naturally derived compound isolated from the thunder god vine (Tripterygium wilfordii Hook. F). Some of these synthesized compounds exhibited antiproliferative activities in the nanomolar range. Among them, compound 33 exhibited both good antiproliferative activity and NO-releasing ability and the acute toxicity of compound 33 decreased more than 160 times (LD = 160.9 mg/kg) than triptolide. Moreover, compound 33 significantly inhibited the growth of melanoma at a low dose (0.3 mg/kg) and showed strong anti-inflammatory activity in vitro and in vivo. These results indicate that compound 33 could be a promising candidate for further study.
|
Antiproliferative activity against human B16-F10 cells assessed as reduction in cell growth incubated for 96 hrs by MTT assay
|
Homo sapiens
|
5.0
nM
|
|
Journal : Eur J Med Chem
Title : Novel nitric oxide-releasing derivatives of triptolide as antitumor and anti-inflammatory agents: Design, synthesis, biological evaluation, and nitric oxide release studies.
Year : 2020
Volume : 190
First Page : 112079
Last Page : 112079
Authors : Zang Y,Lai F,Fu J,Li C,Ma J,Chen C,Liu K,Zhang T,Chen X,Zhang D
Abstract : A series of novel triptolide/furoxans hybrids were designed and synthesized as analogues of triptolide, which is a naturally derived compound isolated from the thunder god vine (Tripterygium wilfordii Hook. F). Some of these synthesized compounds exhibited antiproliferative activities in the nanomolar range. Among them, compound 33 exhibited both good antiproliferative activity and NO-releasing ability and the acute toxicity of compound 33 decreased more than 160 times (LD = 160.9 mg/kg) than triptolide. Moreover, compound 33 significantly inhibited the growth of melanoma at a low dose (0.3 mg/kg) and showed strong anti-inflammatory activity in vitro and in vivo. These results indicate that compound 33 could be a promising candidate for further study.
|
Antiinflammatory activity against mouse RAW264.7 cells assessed as inhibition of LPS-induced TNF-alpha incubated for 1 hr followed by LPS stimulation and measured after 24 hrs by ELISA
|
Mus musculus
|
14.0
nM
|
|
Journal : Eur J Med Chem
Title : Novel nitric oxide-releasing derivatives of triptolide as antitumor and anti-inflammatory agents: Design, synthesis, biological evaluation, and nitric oxide release studies.
Year : 2020
Volume : 190
First Page : 112079
Last Page : 112079
Authors : Zang Y,Lai F,Fu J,Li C,Ma J,Chen C,Liu K,Zhang T,Chen X,Zhang D
Abstract : A series of novel triptolide/furoxans hybrids were designed and synthesized as analogues of triptolide, which is a naturally derived compound isolated from the thunder god vine (Tripterygium wilfordii Hook. F). Some of these synthesized compounds exhibited antiproliferative activities in the nanomolar range. Among them, compound 33 exhibited both good antiproliferative activity and NO-releasing ability and the acute toxicity of compound 33 decreased more than 160 times (LD = 160.9 mg/kg) than triptolide. Moreover, compound 33 significantly inhibited the growth of melanoma at a low dose (0.3 mg/kg) and showed strong anti-inflammatory activity in vitro and in vivo. These results indicate that compound 33 could be a promising candidate for further study.
|
Antiinflammatory activity against mouse RAW264.7 cells assessed as inhibition of LPS-induced IL-6 incubated for 1 hr followed by LPS stimulation and measured after 24 hrs by ELISA
|
Mus musculus
|
23.0
nM
|
|
Journal : Eur J Med Chem
Title : Novel nitric oxide-releasing derivatives of triptolide as antitumor and anti-inflammatory agents: Design, synthesis, biological evaluation, and nitric oxide release studies.
Year : 2020
Volume : 190
First Page : 112079
Last Page : 112079
Authors : Zang Y,Lai F,Fu J,Li C,Ma J,Chen C,Liu K,Zhang T,Chen X,Zhang D
Abstract : A series of novel triptolide/furoxans hybrids were designed and synthesized as analogues of triptolide, which is a naturally derived compound isolated from the thunder god vine (Tripterygium wilfordii Hook. F). Some of these synthesized compounds exhibited antiproliferative activities in the nanomolar range. Among them, compound 33 exhibited both good antiproliferative activity and NO-releasing ability and the acute toxicity of compound 33 decreased more than 160 times (LD = 160.9 mg/kg) than triptolide. Moreover, compound 33 significantly inhibited the growth of melanoma at a low dose (0.3 mg/kg) and showed strong anti-inflammatory activity in vitro and in vivo. These results indicate that compound 33 could be a promising candidate for further study.
|
Antiinflammatory activity against ICR mouse assessed as inhibition of croton oil-induced edema formation at 0.3 mg/kg, po measured after 4 hrs relative to control
|
Mus musculus
|
19.3
%
|
|
Journal : Eur J Med Chem
Title : Novel nitric oxide-releasing derivatives of triptolide as antitumor and anti-inflammatory agents: Design, synthesis, biological evaluation, and nitric oxide release studies.
Year : 2020
Volume : 190
First Page : 112079
Last Page : 112079
Authors : Zang Y,Lai F,Fu J,Li C,Ma J,Chen C,Liu K,Zhang T,Chen X,Zhang D
Abstract : A series of novel triptolide/furoxans hybrids were designed and synthesized as analogues of triptolide, which is a naturally derived compound isolated from the thunder god vine (Tripterygium wilfordii Hook. F). Some of these synthesized compounds exhibited antiproliferative activities in the nanomolar range. Among them, compound 33 exhibited both good antiproliferative activity and NO-releasing ability and the acute toxicity of compound 33 decreased more than 160 times (LD = 160.9 mg/kg) than triptolide. Moreover, compound 33 significantly inhibited the growth of melanoma at a low dose (0.3 mg/kg) and showed strong anti-inflammatory activity in vitro and in vivo. These results indicate that compound 33 could be a promising candidate for further study.
|
Cytotoxicity against human Panc-1 cells incubated for 48 hrs by CCK8 assay
|
Homo sapiens
|
200.0
nM
|
|
Journal : J Med Chem
Title : Development of Potential Antitumor Agents from the Scaffolds of Plant-Derived Terpenoid Lactones.
Year : 2020
Volume : 63
Issue : 24.0
First Page : 15410
Last Page : 15448
Authors : Ren Y,Kinghorn AD
Abstract : Naturally occurring terpenoid lactones and their synthetic derivatives have attracted increasing interest for their promising antitumor activity and potential utilization in the discovery and design of new antitumor agents. In the present perspective article, selected plant-derived five-membered γ-lactones and six-membered δ-lactones that occur with terpenoid scaffolds are reviewed, with their structures, cancer cell line cytotoxicity and in vivo antitumor activity, structure-activity relationships, mechanism of action, and the potential for developing cancer chemotherapeutic agents discussed in each case. The compounds presented include artemisinin (ART, 1), parthenolide (PTL, 2), thapsigargin (TPG, 3), andrographolide (AGL, 4), ginkgolide B (GKL B, 5), jolkinolide B (JKL B, 6), nagilactone E (NGL E, 7), triptolide (TPL, 8), bruceantin (BRC, 9), dichapetalin A (DCT A, 10), and limonin (LMN, 11), and their naturally occurring analogues and synthetic derivatives. It is hoped that this contribution will be supportive of the future development of additional efficacious anticancer agents derived from natural products.
|
Cytotoxicity against human HepG2 cells assessed as inhibition of cell proliferation measured after 48 hrs by MTT assay
|
Homo sapiens
|
33.0
nM
|
|
|
Cytotoxicity against human HL7702 cells assessed as inhibition of cell proliferation measured after 48 hrs by MTT assay
|
Homo sapiens
|
21.0
nM
|
|
|
Cytotoxicity against human PC-3 cells assessed as inhibition of cell proliferation measured after 48 hrs by MTT assay
|
Homo sapiens
|
21.0
nM
|
|
|
Cytotoxicity against human HeLa cells assessed as inhibition of cell proliferation measured after 48 hrs by MTT assay
|
Homo sapiens
|
43.0
nM
|
|
|
Cytotoxicity against human MCF7 cells assessed as inhibition of cell proliferation measured after 48 hrs by MTT assay
|
Homo sapiens
|
22.0
nM
|
|
|
Cytotoxicity against human PANC-1 cells assessed as inhibition of cell proliferation measured after 48 hrs by MTT assay
|
Homo sapiens
|
56.0
nM
|
|
|
Cytotoxicity against human HBE cells assessed as inhibition of cell proliferation measured after 48 hrs by MTT assay
|
Homo sapiens
|
30.0
nM
|
|
|
Cytotoxicity against human NCI-H1299 cells assessed as inhibition of cell proliferation measured after 48 hrs by MTT assay
|
Homo sapiens
|
49.0
nM
|
|
|
Cytotoxicity against human NCI-H1975 cells assessed as inhibition of cell proliferation measured after 48 hrs by MTT assay
|
Homo sapiens
|
19.0
nM
|
|
