|
Antiinflammatory activity against D-adjuvant arthritis in injected rat paw at the dose of 25 mg/kg by oral administration
|
Rattus norvegicus
|
86.0
%
|
|
Journal : J. Med. Chem.
Title : Bis basic substituted diaminobenzobisthiazoles as potential antiarthritic agents.
Year : 1992
Volume : 35
Issue : 2
First Page : 350
Last Page : 361
Authors : Cullen E, Becker R, Freter K, LeClerq T, Possanza G, Wong HC.
Abstract : A series of benzobisthiazoles were screened for antiinflammatory activity in the carrageenan paw edema and adjuvant arthritis tests. Compound 26, 2,6-bis(N,N-diethylamino)benzo[1,2-d:5,4-d']bisthiazole, was found to inhibit the swelling of the uninjected paw in the prophylactic adjuvant arthritis model with an ED50 of 2.3 mg/kg orally. As with most compounds of this series, 26 was inactive in acute model of inflammation, such as paw edema; like steroids, it showed activity in the granuloma pouch assay but did not inhibit cyclooxygenase, indicating a mode of action different from the classical nonsteroidal antiinflammatory drugs (NSAID's). At doses higher than those producing antiinflammatory activity, 26 had some immunoregulating properties.
|
Antiinflammatory activity against D-adjuvant arthritis in uninjected rat paw at the dose of 25 mg/kg by oral administration
|
Rattus norvegicus
|
100.0
%
|
|
Journal : J. Med. Chem.
Title : Bis basic substituted diaminobenzobisthiazoles as potential antiarthritic agents.
Year : 1992
Volume : 35
Issue : 2
First Page : 350
Last Page : 361
Authors : Cullen E, Becker R, Freter K, LeClerq T, Possanza G, Wong HC.
Abstract : A series of benzobisthiazoles were screened for antiinflammatory activity in the carrageenan paw edema and adjuvant arthritis tests. Compound 26, 2,6-bis(N,N-diethylamino)benzo[1,2-d:5,4-d']bisthiazole, was found to inhibit the swelling of the uninjected paw in the prophylactic adjuvant arthritis model with an ED50 of 2.3 mg/kg orally. As with most compounds of this series, 26 was inactive in acute model of inflammation, such as paw edema; like steroids, it showed activity in the granuloma pouch assay but did not inhibit cyclooxygenase, indicating a mode of action different from the classical nonsteroidal antiinflammatory drugs (NSAID's). At doses higher than those producing antiinflammatory activity, 26 had some immunoregulating properties.
|
Antiinflammatory activity dosed orally against carrageenan induced rat paw edema(CPE)
|
Rattus norvegicus
|
18.0
%
|
|
Journal : J. Med. Chem.
Title : Bis basic substituted diaminobenzobisthiazoles as potential antiarthritic agents.
Year : 1992
Volume : 35
Issue : 2
First Page : 350
Last Page : 361
Authors : Cullen E, Becker R, Freter K, LeClerq T, Possanza G, Wong HC.
Abstract : A series of benzobisthiazoles were screened for antiinflammatory activity in the carrageenan paw edema and adjuvant arthritis tests. Compound 26, 2,6-bis(N,N-diethylamino)benzo[1,2-d:5,4-d']bisthiazole, was found to inhibit the swelling of the uninjected paw in the prophylactic adjuvant arthritis model with an ED50 of 2.3 mg/kg orally. As with most compounds of this series, 26 was inactive in acute model of inflammation, such as paw edema; like steroids, it showed activity in the granuloma pouch assay but did not inhibit cyclooxygenase, indicating a mode of action different from the classical nonsteroidal antiinflammatory drugs (NSAID's). At doses higher than those producing antiinflammatory activity, 26 had some immunoregulating properties.
|
Antitumor activity against S180 cells implanted in mouse at 30 mg/kg, ip
|
Mus musculus
|
72.94
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Novel class of cyclophosphamide prodrug: cyclophosphamide spiropiperaziniums (CPSP).
Year : 2006
Volume : 16
Issue : 14
First Page : 3727
Last Page : 3730
Authors : Sun Q, Li RT, Guo W, Cui JR, Cheng TM, Ge ZM.
Abstract : A novel class of cyclophosphamide spiropiperaziniums was synthesized and evaluated for their in vivo anti-cancer activities against S180 and H22. Most of them exhibited definite activities. Especially, compounds 8b and 8k showed good anti-cancer activities, meanwhile, 8k also showed much lower toxicity than CP. Several interesting structure-activity relationships were revealed.
|
Antitumor activity against H22 cells implanted in mouse at 30 mg/kg, ip
|
Mus musculus
|
72.02
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Novel class of cyclophosphamide prodrug: cyclophosphamide spiropiperaziniums (CPSP).
Year : 2006
Volume : 16
Issue : 14
First Page : 3727
Last Page : 3730
Authors : Sun Q, Li RT, Guo W, Cui JR, Cheng TM, Ge ZM.
Abstract : A novel class of cyclophosphamide spiropiperaziniums was synthesized and evaluated for their in vivo anti-cancer activities against S180 and H22. Most of them exhibited definite activities. Especially, compounds 8b and 8k showed good anti-cancer activities, meanwhile, 8k also showed much lower toxicity than CP. Several interesting structure-activity relationships were revealed.
|
Antitumor activity in H22 cells xenografted ICR mouse assessed as tumor growth inhibition at 30 mg/kg, iv after 4 days
|
Mus musculus
|
56.3
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Synthesis and cytotoxic activity of 17-carboxylic acid modified 23-hydroxy betulinic acid ester derivatives.
Year : 2007
Volume : 17
Issue : 5
First Page : 1475
Last Page : 1478
Authors : Bi Y, Xu J, Wu X, Ye W, Yuan S, Zhang L.
Abstract : New 17-carboxylic acid modified 23-hydroxy betulinic acid ester derivatives were prepared and tested for cytotoxic activity on five cancer cell lines in vitro: all tested compounds showed stronger cytotoxic activity than 23-hydroxy betulinic acid and betulinic acid. In addition, compound 5a was tested for anti-tumor activity in vivo: it had much better anti-tumor activity than 23-OH betulinic acid and had similar anti-tumor activity with cyclophosphamide and 5-fluorouracil.
|
Antitumor activity in mouse xenografted with S180 cells assessed as inhibition of tumor growth at 30 mg/kg/day, ip after 10 days
|
Mus musculus
|
63.5
%
|
|
Journal : Bioorg. Med. Chem.
Title : Synthesis and biological evaluation of imidazol-2-one derivatives as potential antitumor agents.
Year : 2008
Volume : 16
Issue : 5
First Page : 2550
Last Page : 2557
Authors : Xue N, Yang X, Wu R, Chen J, He Q, Yang B, Lu X, Hu Y.
Abstract : A new series of aryl substituted imidazol-2-one derivatives structurally related to combretastatin A-4 (CA-4) were synthesized and evaluated for their cytotoxic activities in vitro against various human cancer cell lines including MDR cell line. The cytotoxic effects of compounds 7b and 7i proved to be similar to or greater than that of docetaxel. The highly active compound 7b also exhibited excellent inhibitory activity on tumor growth in vivo.
|
Antitumor activity in mouse xenografted with H22 cells assessed as inhibition of tumor growth at 30 mg/kg/day, ip after 10 days
|
Mus musculus
|
36.2
%
|
|
Journal : Bioorg. Med. Chem.
Title : Synthesis and biological evaluation of imidazol-2-one derivatives as potential antitumor agents.
Year : 2008
Volume : 16
Issue : 5
First Page : 2550
Last Page : 2557
Authors : Xue N, Yang X, Wu R, Chen J, He Q, Yang B, Lu X, Hu Y.
Abstract : A new series of aryl substituted imidazol-2-one derivatives structurally related to combretastatin A-4 (CA-4) were synthesized and evaluated for their cytotoxic activities in vitro against various human cancer cell lines including MDR cell line. The cytotoxic effects of compounds 7b and 7i proved to be similar to or greater than that of docetaxel. The highly active compound 7b also exhibited excellent inhibitory activity on tumor growth in vivo.
|
Antitumor activity in mouse H22 cell xenografted mouse at 20 mg/kg/day, iv after 4 days
|
Mus musculus
|
54.3
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Synthesis and biological evaluation of novel 1-O- and 14-O-derivatives of oridonin as potential anticancer drug candidates.
Year : 2008
Volume : 18
Issue : 16
First Page : 4741
Last Page : 4744
Authors : Xu J, Yang J, Ran Q, Wang L, Liu J, Wang Z, Wu X, Hua W, Yuan S, Zhang L, Shen M, Ding Y.
Abstract : Novel 1-O- and 14-O-derivatives of oridonin were synthesized and biologically evaluated. All of the derivatives exhibited stronger cytotoxicity against six cancer cell lines (BGC-7901, SW-480, HL-60, BEL-7402, A549, and B16) than oridonin in vitro, and some of them were more potent than oridonin and cyclophosphamide in vivo. Compounds Ib and IIg were the most potent with the IC(50) values of 0.84 microM for Ib in HL-60 cell and 1.00 microM for IIg in BEL-7402 cell.
|
Inhibition of 4-(4-(dimethylamino)styryl)-N-methylpyridinium uptake at human OCT1 expressed in HEK293 cells at 100 uM by confocal microscopy
|
Homo sapiens
|
4.7
%
|
|
Journal : J. Med. Chem.
Title : Structural requirements for drug inhibition of the liver specific human organic cation transport protein 1.
Year : 2008
Volume : 51
Issue : 19
First Page : 5932
Last Page : 5942
Authors : Ahlin G, Karlsson J, Pedersen JM, Gustavsson L, Larsson R, Matsson P, Norinder U, Bergström CA, Artursson P.
Abstract : The liver-specific organic cation transport protein (OCT1; SLC22A1) transports several cationic drugs including the antidiabetic drug metformin and the anticancer agents oxaliplatin and imatinib. In this study, we explored the chemical space of registered oral drugs with the aim of studying the inhibition pattern of OCT1 and of developing predictive computational models of OCT1 inhibition. In total, 191 structurally diverse compounds were examined in HEK293-OCT1 cells. The assay identified 47 novel inhibitors and confirmed 15 previously known inhibitors. The enrichment of OCT1 inhibitors was seen in several drug classes including antidepressants. High lipophilicity and a positive net charge were found to be the key physicochemical properties for OCT1 inhibition, whereas a high molecular dipole moment and many hydrogen bonds were negatively correlated to OCT1 inhibition. The data were used to generate OPLS-DA models for OCT1 inhibitors; the final model correctly predicted 82% of the inhibitors and 88% of the noninhibitors of the test set.
|
Antitumor activity against mouse S180 cells xenografted in ICR mouse assessed as inhibition of tumor weight at 100 mg/kg, ig administered 2 days after tumor inoculation qd for 7 days relative to control
|
Mus musculus
|
74.5
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Synthesis and anticancer evaluation of alpha-lipoic acid derivatives.
Year : 2010
Volume : 20
Issue : 10
First Page : 3078
Last Page : 3083
Authors : Zhang SJ, Ge QF, Guo DW, Hu WX, Liu HZ.
Abstract : alpha-Lipoic acid derivatives were synthesized and evaluated for their in vitro anticancer activities against NCI-460, HO-8910, KB, BEL-7402, and PC-3 cell lines. The results, for most compounds exhibited dose-dependent inhibitory property and several compounds had good inhibitions at the dose of 100 microg/mL. Compound 17 m was further selected for in vivo evaluation against S180 xenograft in ICR mice, which had 24.7% tumor-weight inhibition through intragastric administration of 200mg/kg of body weight. Moreover, the LD(50) in mice for 17 m through ig exceeded 1000 mg/kg of body weight.
|
Anticancer activity against mouse S180 cells xenografted in ICR mouse assessed as tumor weight inhibition at 100 mg/kg, ip relative to control
|
Mus musculus
|
91.68
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Synthesis and anticancer evaluation of thiazolyl-chalcones.
Year : 2010
Volume : 20
Issue : 22
First Page : 6555
Last Page : 6559
Authors : Shi HB, Zhang SJ, Ge QF, Guo DW, Cai CM, Hu WX.
Abstract : Thirty-seven (E)-1-(4-methyl-2-arylaminothiazol-5-yl)-3-arylprop-2-en-1-ones were synthesized via Claisen-Schmidt condensation of 1-(4-methyl-2-(arylamino)thiazol-5-yl)ethanone with the corresponding arylaldehydes. All these thiazolyl-chalcones were characterized and evaluated by MTT assay on human cancer cell lines BGC-823, PC-3, NCI-H460, BEL-7402 in vitro. Compounds 5, 8, 26, 37 and 41 are effective against cancer cell lines with IC(50)s below 10 μM. The antitumor activity in ICR mice bearing sarcoma 180 tumors indicates compounds 10 and 41 have moderate in vivo activity with 22-25% tumor-weight inhibition.
|
Antitumor activity against mouse S180 cells xenografted in Kunming mouse assessed as tumor growth inhibition rate at 20 mg/kg, po administered for 10 days relative to control
|
Mus musculus
|
81.72
%
|
|
Journal : Eur. J. Med. Chem.
Title : Biological evaluation of polyhalo 1,3-diazaheterocycle fused isoquinolin-1(2H)-imine derivatives.
Year : 2011
Volume : 46
Issue : 4
First Page : 1172
Last Page : 1180
Authors : Huang C, Yan SJ, Zeng XH, Dai XY, Zhang Y, Qing C, Lin J.
Abstract : A series of polyhalo 1,3-diazaheterocycle fused isoquinolin-1(2H)-imines were evaluated in vitro against human tumour cell lines including A431, K562, HL60, HepG2 and Skov-3. As a result, some of the target compounds such as 5b, 5c, 5i, 5o, 6c, 6h and 7f showed stronger cytotoxicity against K562, H562 and Skov-3 cells in comparison with cisplatin, and the others displayed moderate cytotoxicity to A431 and HepG2. Biological investigations using the representative compounds 5c, 6c and 6h were also performed in mice bearing S(180) and H(22) tumours. The results indicated that these three compounds inhibit S(180) and H(22) growth. In addition, compounds 6c and 6h have very low acute toxicities. The preliminary analysis of structure-activity relationships is also discussed.
|
Antitumor activity against mouse H22 cells xenografted in Kunming mouse assessed as tumor growth inhibition rate at 20 mg/kg, po administered for 10 days relative to control
|
Mus musculus
|
56.24
%
|
|
Journal : Eur. J. Med. Chem.
Title : Biological evaluation of polyhalo 1,3-diazaheterocycle fused isoquinolin-1(2H)-imine derivatives.
Year : 2011
Volume : 46
Issue : 4
First Page : 1172
Last Page : 1180
Authors : Huang C, Yan SJ, Zeng XH, Dai XY, Zhang Y, Qing C, Lin J.
Abstract : A series of polyhalo 1,3-diazaheterocycle fused isoquinolin-1(2H)-imines were evaluated in vitro against human tumour cell lines including A431, K562, HL60, HepG2 and Skov-3. As a result, some of the target compounds such as 5b, 5c, 5i, 5o, 6c, 6h and 7f showed stronger cytotoxicity against K562, H562 and Skov-3 cells in comparison with cisplatin, and the others displayed moderate cytotoxicity to A431 and HepG2. Biological investigations using the representative compounds 5c, 6c and 6h were also performed in mice bearing S(180) and H(22) tumours. The results indicated that these three compounds inhibit S(180) and H(22) growth. In addition, compounds 6c and 6h have very low acute toxicities. The preliminary analysis of structure-activity relationships is also discussed.
|
Antitumor activity against mouse H22 tumor-nearing ICR mouse assessed as inhibition of tumor growth at 10 mg/kg, ip for 7 days measured on day 9
|
Mus musculus
|
41.74
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : A novel, broad-spectrum antitumor compound containing the 1-hydroxycyclohexa-2,5-dien-4-one group: the disclosure of a new antitumor pharmacophore in protoapigenone 1.
Year : 2011
Volume : 21
Issue : 11
First Page : 3427
Last Page : 3430
Authors : Yuan Q, Liu Z, Xiong C, Wu L, Wang J, Ruan J.
Abstract : The synthesis of a new compound 9 containing the 4-hydroxy-2,5-cyclohexadien-1-one system, a key elements toward elucidation of the protoapigenone 1 antitumor pharmacophore, was described. The compound showed potent in vitro antitumor potency with low micromolar IC(50)'s against breast, ovarian, prostate, liver, pancreas, and blood cancer cell lines tested and could inhibit tumor growth in vivo but no significant impairment of hematopoiesis or immune function was observed. The minimum structural pharmacophore of 1 has now been refined.
|
Antitumor activity against mouse H22 cells xenografted in kunming mouse assessed as inhibition of tumor growth at 15 mg/kg, ip for 7 days
|
Mus musculus
|
55.0
%
|
|
Journal : Eur. J. Med. Chem.
Title : In vitro and in vivo anticancer activity evaluation of ursolic acid derivatives.
Year : 2011
Volume : 46
Issue : 7
First Page : 2652
Last Page : 2661
Authors : Shao JW, Dai YC, Xue JP, Wang JC, Lin FP, Guo YH.
Abstract : Twenty-three ursolic acid (1) derivatives 2-24 (ten novel compounds 8-10, 14-17 and 22-24) modified at the C-3 and the C-28 positions were synthesized, and their structures were confirmed by IR, (1)H NMR, MS, and elemental analysis. The single crystals of compounds 15 and 17 were obtained. The cytotoxic activity of the derivatives was evaluated against HepG2, BGC-823, SH-SY5Y, HeLa and HELF cells by the MTT assay. The induction of apoptosis and affects on the cell cycle distribution with compound 14 were assessed by fluorescence microscopy, flow cytometry and the activity of caspase-3 in HepG2 cells. Compounds 14-17 had more significant antiproliferative ability against the four cancer cell lines and low cytotoxicity to human embryonic lung fibroblast cells (HELF). Compounds 11, 14-16, 21 and 23 were particularly active against HepG2 cell growth. Compound 14 was selected to investigate cell apoptosis and cell cycle distribution. Flow cytometric analysis and morphologic changes of the cell exhibited that treatment of HepG2 cells with compound 14 led to cell apoptosis accompanied by cell cycle arrest at the S phase in a dose-dependent manner. Furthermore, the activity of the caspase-3 enzyme was increased in the treated cells. In vivo studies using H22 xenografts in Kunming mice were conducted with compound 14 at doses of 50, 100 and 150 mg/kg body weight. The results revealed that the medium dosage group (100 mg/kg) showed significant anticancer activity (45.6 ± 4.3%) compared to the control group.
|
Antitumor activity against human H22 cells xenografted in Kunming mouse assessed as reduction in tumor volume at 20 mg/kg, po qd for 10 days
|
Homo sapiens
|
72.0
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Structural modification of ginsenoside Rh(2) by fatty acid esterification and its detoxification property in antitumor.
Year : 2012
Volume : 22
Issue : 2
First Page : 1082
Last Page : 1085
Authors : Wei GQ, Zheng YN, Li W, Liu WC, Lin T, Zhang WY, Chen HF, Zeng JZ, Zhang XK, Chen QC.
Abstract : Ginsenoside Rh(2), one of the most important ginsenosides with anticancer properties in red ginseng, has been developed as principal antitumor ingredient for clinical use. However, the cytotoxicity test in human hepatocyte cell line QSG-7701 (IC(50) 37.3μM) indicated that Rh(2) might show strong cytotoxic side-effect on the normal liver cells. For blunting the toxicity, Rh(2) was structurally modified by reacting with octanoyl chloride to give a dioctanoyl ester of Rh(2) (D-Rh(2)) in the present study. MTT assay in QSG-7701 cell line in vitro showed that the cytotoxicity of D-Rh(2) on human hepatocyte cells (IC(50) 80.5μM) was significantly lower than that of Rh(2). While antitumor xenograft assay in mice bearing H22 liver cancer cells in vivo showed that the antitumor activity of D-Rh(2) retained to be strong as that of Rh(2). According to previous pharmacokinetic studies, the fatty acid esterification of Rh(2) might be of detoxification reaction to cells. Additionally, D-Rh(2) showed significant enhancement on increasing thymus index at the dose of 10mg/kg compared with vehicle treated control group. Thus, D-Rh(2) might indirectly affect tumor growth by stimulating lymphocytes to become cytotoxic to tumor cells. Finally, our findings suggested that D-Rh(2), the fatty acid ester of Rh(2), might attenuate the side-effect by detoxification to human normal cell and could be a more potential candidate for developing as an antitumor drug.
|
Cytotoxicity against Homo sapiens (human) MDA-MB-231 cells after 48 hr by MTT assay
|
Homo sapiens
|
90.0
nM
|
|
Journal : Med Chem Res
Title : Antitumor activities of some new 1,3,2-oxaza- and 1,3,2-diazaphosphorinanes against K562, MDA-MB-231, and HepG2 cells
Year : 2012
Volume : 21
Issue : 9
First Page : 2185
Last Page : 2195
Authors : Gholivand K, Ghaziani F, Shariatinia Z, Dorosti N, Mirshahi M, Sarikhani S
|
Cytotoxicity against Homo sapiens (human) HepG2 cells after 48 hr by MTT assay
|
Homo sapiens
|
240.0
nM
|
|
Journal : Med Chem Res
Title : Antitumor activities of some new 1,3,2-oxaza- and 1,3,2-diazaphosphorinanes against K562, MDA-MB-231, and HepG2 cells
Year : 2012
Volume : 21
Issue : 9
First Page : 2185
Last Page : 2195
Authors : Gholivand K, Ghaziani F, Shariatinia Z, Dorosti N, Mirshahi M, Sarikhani S
|
Cytotoxicity against Homo sapiens (human) K562 cells after 48 hr by MTT assay
|
Homo sapiens
|
150.0
nM
|
|
Journal : Med Chem Res
Title : Antitumor activities of some new 1,3,2-oxaza- and 1,3,2-diazaphosphorinanes against K562, MDA-MB-231, and HepG2 cells
Year : 2012
Volume : 21
Issue : 9
First Page : 2185
Last Page : 2195
Authors : Gholivand K, Ghaziani F, Shariatinia Z, Dorosti N, Mirshahi M, Sarikhani S
|
Antiproliferative activity against Homo sapiens (human) K562 cells after 48 hr by MTT assay
|
Homo sapiens
|
153.0
nM
|
|
Journal : Med Chem Res
Title : Cyclophosphamide analogues: synthesis, spectroscopic study, and antitumor activity of diazaphosphorinanes
Year : 2011
Volume : 20
Issue : 8
First Page : 1287
Last Page : 1293
Authors : Gholivand K, Dorosti N, Shariatinia Z, Ghaziany F, Sarikhani S, Mirshahi M
|
Cytotoxicity against Homo sapiens (human) MCF7 cells after 48 hr by trypan blue assay
|
Homo sapiens
|
160.0
nM
|
|
Journal : Med Chem Res
Title : Synthesis, chemical characterization of novel 1,3-dimethyl acridones as cytotoxic agents, and their DNA-binding studies
Year : 2010
Volume : 19
Issue : 7
First Page : 674
Last Page : 689
Authors : Sathish NK, GopKumar P, Rajendra Prasad VVS, Shanta Kumar SM, Mayur YC
|
Antitumor activity against mouse LLC cells xenografted in mouse assessed as tumor inhibition at 30 mg/kg, ip qd for 7 days measured every 3 days for 21 days
|
Mus musculus
|
85.6
%
|
|
Journal : Eur. J. Med. Chem.
Title : Synthesis and structure-activity relationships of harmine derivatives as potential antitumor agents.
Year : 2013
Volume : 60
First Page : 135
Last Page : 143
Authors : Cao R, Fan W, Guo L, Ma Q, Zhang G, Li J, Chen X, Ren Z, Qiu L.
Abstract : Harmine, a naturally occurring β-carboline alkaloid, showed good antitumor activities together with remarkable neurotoxic effects in animal models. In order to search for novel leading compounds endowed with better antitumor activities and less neurotoxicities, a series of harmine derivatives were designed and synthesized by modification of position-2, 7 and 9 of β-carboline nucleus, and their cytotoxic activities against human tumor cell lines were investigated. Acute toxicities and antitumor activities of the selected compounds in mice were also evaluated. Structure-activity relationships studies confirmed that (1) the 7-methoxy structural moiety was the pharmacophore responsible for the neurotoxic effects of this class of compounds; (2) the substituents in position-2 and 9 played a vital role in modulation of their antitumor activities.
|
Antitumor activity against mouse Sarcoma 180 cells xenografted in mouse assessed as tumor inhibition at 30 mg/kg, ip qd for 7 days measured every 3 days for 21 days
|
Mus musculus
|
88.7
%
|
|
Journal : Eur. J. Med. Chem.
Title : Synthesis and structure-activity relationships of harmine derivatives as potential antitumor agents.
Year : 2013
Volume : 60
First Page : 135
Last Page : 143
Authors : Cao R, Fan W, Guo L, Ma Q, Zhang G, Li J, Chen X, Ren Z, Qiu L.
Abstract : Harmine, a naturally occurring β-carboline alkaloid, showed good antitumor activities together with remarkable neurotoxic effects in animal models. In order to search for novel leading compounds endowed with better antitumor activities and less neurotoxicities, a series of harmine derivatives were designed and synthesized by modification of position-2, 7 and 9 of β-carboline nucleus, and their cytotoxic activities against human tumor cell lines were investigated. Acute toxicities and antitumor activities of the selected compounds in mice were also evaluated. Structure-activity relationships studies confirmed that (1) the 7-methoxy structural moiety was the pharmacophore responsible for the neurotoxic effects of this class of compounds; (2) the substituents in position-2 and 9 played a vital role in modulation of their antitumor activities.
|
Antitumor activity against human H22 cells transplanted in ICR mouse assessed as tumor growth inhibition at 30 mg/kg, iv administered 7 days post tumor transplantation
|
Homo sapiens
|
53.7
%
|
|
Journal : Eur. J. Med. Chem.
Title : Synthesis and antitumor activity of novel 3-oxo-23-hydroxybetulinic acid derivatives.
Year : 2014
Volume : 87
First Page : 159
Last Page : 167
Authors : Zhang H, Zhu P, Liu J, Yang X, Xu S, Yao H, Jiang J, Ye W, Wu X, Xu J.
Abstract : A series of novel derivatives of 3-oxo-23-hydroxybetulinic acid was designed, synthesized, and evaluated for their antiproliferative activity against a panel of cancer cell lines (HL-60, BEL-7402, SF-763, HeLa, B16 and A375). The results indicated that majority of the derivatives exhibited more significant antitumor activity than the parent compound. In particular compound 10e showed the most potent activity with IC50 values of 5.85, 6.23 and 7.22 μM against B16, SF-763 and BEL-7402 cells, respectively. Furthermore, 10e inhibited tumor growth by 51.8% and 62.7% (w/w) in H22 and B16 xenograft mouse models, comparable to cyclophosphamide and 5-fluorouracil, respectively.
|
Antitumor activity against human H22 cells xenografted in ICR mouse assessed as tumor growth inhibition at 30 mg/kg, iv administered 7 days post inoculation measured at day 25 of tumor transplantation
|
Homo sapiens
|
53.7
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Synthesis, in vitro and in vivo antitumor activity of pyrazole-fused 23-hydroxybetulinic acid derivatives.
Year : 2015
Volume : 25
Issue : 3
First Page : 728
Last Page : 732
Authors : Zhang H, Zhu P, Liu J, Lin Y, Yao H, Jiang J, Ye W, Wu X, Xu J.
Abstract : A collection of pyrazole-fused 23-hydroxybetulinic acid derivatives were designed, synthesized and evaluated for their antitumor activity. Most of the newly synthesized compounds exhibited significant antiproliferative activity. Especially compound 15e displayed the most potent activity with the IC50 values of 5.58 and 6.13μM against B16 and SF763 cancer cell lines, respectively. Furthermore, the significant in vivo antitumor activity of 15e was validated in H22 liver cancer and B16 melanoma xenograft mouse models. The structure-activity relationships of these 23-hydroxybetulinic acid derivatives were also discussed based on the present investigation.
|
Antitumor activity against mouse S180 cells implanted in mouse assessed as inhibition of tumor growth at 40 mg/kg
|
Mus musculus
|
54.8
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Synthesis and antitumor activity of feruloyl and caffeoyl derivatives.
Year : 2014
Volume : 24
Issue : 18
First Page : 4367
Last Page : 4371
Authors : Chen HZ, Chen YB, Lv YP, Zeng F, Zhang J, Zhou YL, Li HB, Chen LF, Zhou BJ, Gao JR, Xia CN.
Abstract : We developed two efficient protocols for the synthesis of feruloyl and caffeoyl derivatives from commercial vanillin and veratraldehyde. Pharmacological activities were assessed against a panel of human cancer cell lines in vitro. Most synthesized compounds demonstrated attractive cytotoxicity. Several new compounds demonstrated significant antiproliferative and cytotoxic activities against HeLa and Bewo tumor cell lines. In particular, 5-nitro caffeic adamantyl ester showed broad spectrum of tumor inhibition in 10 cell lines, and reduced tumor weight by 36.7% in vivo when administered at a dose of 40 mg kg(-1).
|
In vivo antitumor activity against human H22 cells xenografted in mouse assessed as tumor growth inhibitory ratio at 30 mg/kg, ip administered after 7 days of tumor transplantation measured at 25th day after tumor inoculation
|
Homo sapiens
|
53.7
%
|
|
Journal : Eur. J. Med. Chem.
Title : Design, synthesis and antitumor activity of triterpenoid pyrazine derivatives from 23-hydroxybetulinic acid.
Year : 2015
Volume : 97
First Page : 235
Last Page : 244
Authors : Zhang H, Wang Y, Zhu P, Liu J, Xu S, Yao H, Jiang J, Ye W, Wu X, Xu J.
Abstract : Pyrazine-fused 23-hydroxybetulinic acid was synthesized by introducing a pyrazine ring between C-2 and C-3 position and further modifications were carried out by substitution of C-28 carboxyl group by ester and amide linkage to enhance the antitumor activity. The biological screening results showed that all of the derivatives exhibited more significant antiproliferative activity than the parent compound. In particular compound 12a exhibited the most potent activity with IC50 values of 3.53 μM, 4.42 μM and 5.13 μM against cell lines SF-763, B16 and Hela, respectively. In the preliminary mechanism study, 12a caused cell arrest in G1 phase and significantly induced apoptosis of B16 cells in a dose-dependent manner. Furthermore, the in vivo antitumor activity of 12a was validated (tumor inhibitory ratio of 55.6% and 62.7%, respectively) in mice with H22 liver cancer and B16 melanoma.
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Antibacterial activity against Staphylococcus aureus MRSA ATCC 43300 (CO-ADD:GP_020); MIC in CAMBH media, using NBS plates, by OD(600)
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Staphylococcus aureus subsp. aureus
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2.64
%
|
|
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Antibacterial activity against Escherichia coli ATCC 25922 (CO-ADD:GN_001); MIC in CAMBH media using NBS plates, by OD(600)
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Escherichia coli
|
1.99
%
|
|
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Antibacterial activity against Klebsiella pneumoniae MDR ATCC 70063 (CO-ADD:GN_003); MIC in CAMBH media using NBS plates, by OD(600)
|
Klebsiella pneumoniae
|
1.43
%
|
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Antibacterial activity against Klebsiella pneumoniae MDR ATCC 70063 (CO-ADD:GN_003); MIC in CAMBH media using NBS plates, by OD(600)
|
Klebsiella pneumoniae
|
7.22
%
|
|
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Antibacterial activity against Pseudomonas aeruginosa ATCC 27853 (CO-ADD:GN_042); MIC in CAMBH media using NBS plates, by OD(600)
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Pseudomonas aeruginosa
|
15.65
%
|
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Antibacterial activity against Pseudomonas aeruginosa ATCC 27853 (CO-ADD:GN_042); MIC in CAMBH media using NBS plates, by OD(600)
|
Pseudomonas aeruginosa
|
4.42
%
|
|
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Antibacterial activity against Acinetobacter baumannii ATCC 19606 (CO-ADD:GN_034); MIC in CAMBH media using NBS plates, by OD600
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Acinetobacter baumannii
|
0.33
%
|
|
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Antifungal activity against Candida albicans ATCC 90028 (CO-ADD:FG_001); MIC in YNB media using NBS plates, by OD630
|
Candida albicans
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-2.64
%
|
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Antifungal activity against Candida albicans ATCC 90028 (CO-ADD:FG_001); MIC in YNB media using NBS plates, by OD630
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Candida albicans
|
0.13
%
|
|
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Antifungal activity against Cryptococcus neoformans H99 ATCC 208821 (CO-ADD:FG_002); MIC in YNB media using NBS plates, by Resazurin OD(600-570)
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Cryptococcus neoformans
|
-8.46
%
|
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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
|
1.2
%
|
|
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Antibacterial activity against Staphylococcus aureus MRSA ATCC 43300 (CO-ADD:GP_020); MIC in CAMBH media using NBS plates, by Resazurin F(560/590)
|
Staphylococcus aureus subsp. aureus
|
22.17
%
|
|
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Antibacterial activity against Acinetobacter baumannii ATCC 19606 (CO-ADD:GN_034); MIC in CAMBH media using NBS plates, by Resazurin F(560/590)
|
Acinetobacter baumannii
|
-9.14
%
|
|
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Antibacterial activity against Escherichia coli ATCC 25922 (CO-ADD:GN_001); MIC in CAMBH media using NBS plates, by Resazurin F(560/590)
|
Escherichia coli
|
1.21
%
|
|
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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
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Homo sapiens
|
-5.32
%
|
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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.
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SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate
|
Severe acute respiratory syndrome coronavirus 2
|
24.47
%
|
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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.
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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
|
0.2
%
|
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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
|
0.2
%
|
|
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.
