|
Cytotoxicity against chronic myelogenous leukemia cell line K-562 was determined by measuring [3H]thymidine incorporation after 48 h
|
Homo sapiens
|
0.4
ug.mL-1
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Cytotoxic and antibacterial activity of 2-oxopurine derivatives.
Year : 2002
Volume : 12
Issue : 4
First Page : 567
Last Page : 569
Authors : Andresen G, Gundersen LL, Nissen-Meyer J, Rise F, Spilsberg B.
Abstract : Initial screening of the cytotoxic and antibacterial properties of 6-substituted 2-oxopurines and dihydro-2-oxopurines revealed that several compounds exhibited cytotoxicity against K-562 cells in the same range as the well known antileukemic drug 6-mercaptopurine. Most compounds were also tested for inhibitory effect on a Gram-positive bacterium, Lactobacillus casei, as well as the mycobacterium Mycobacterium tuberculosis. Generally the 2-oxopurines exhibited low antibacterial effect.
|
Cytotoxicity against chronic myelogenous leukemia cell line K-562 was determined by measuring [3H]thymidine incorporation after 5 h
|
Homo sapiens
|
8.5
ug.mL-1
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Cytotoxic and antibacterial activity of 2-oxopurine derivatives.
Year : 2002
Volume : 12
Issue : 4
First Page : 567
Last Page : 569
Authors : Andresen G, Gundersen LL, Nissen-Meyer J, Rise F, Spilsberg B.
Abstract : Initial screening of the cytotoxic and antibacterial properties of 6-substituted 2-oxopurines and dihydro-2-oxopurines revealed that several compounds exhibited cytotoxicity against K-562 cells in the same range as the well known antileukemic drug 6-mercaptopurine. Most compounds were also tested for inhibitory effect on a Gram-positive bacterium, Lactobacillus casei, as well as the mycobacterium Mycobacterium tuberculosis. Generally the 2-oxopurines exhibited low antibacterial effect.
|
Inhibitory concentration required against human chronic myelogenous leukemic K-562 cell line after 48h, using [3H]thymidine incorporation assay
|
Homo sapiens
|
0.6
ug.mL-1
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Cytotoxic activity of 6-alkynyl- and 6-alkenylpurines.
Year : 2003
Volume : 13
Issue : 5
First Page : 877
Last Page : 880
Authors : Bråthe A, Gundersen LL, Nissen-Meyer J, Rise F, Spilsberg B.
Abstract : 6-Alkynyl- and 6-alkenylpurines have been screened for cytotoxic activity against a human chronic myelogenous leukemia cell line; K-562 cells using a [(3)H]-thymidine incorporation assay. Most alkynes displayed cytotoxicity comparable to, or better than, the known anticancer drugs 6-mercaptopurine and fludarabine. The 6-alkenylpurines, which are promising plant growth stimulators and 15-lipoxygenase inhibitors, exhibited only low toxicity.
|
Inhibitory concentration required against human chronic myelogenous leukemic K-562 cell line after 5h, using [3H]thymidine incorporation assay
|
Homo sapiens
|
10.0
ug.mL-1
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Cytotoxic activity of 6-alkynyl- and 6-alkenylpurines.
Year : 2003
Volume : 13
Issue : 5
First Page : 877
Last Page : 880
Authors : Bråthe A, Gundersen LL, Nissen-Meyer J, Rise F, Spilsberg B.
Abstract : 6-Alkynyl- and 6-alkenylpurines have been screened for cytotoxic activity against a human chronic myelogenous leukemia cell line; K-562 cells using a [(3)H]-thymidine incorporation assay. Most alkynes displayed cytotoxicity comparable to, or better than, the known anticancer drugs 6-mercaptopurine and fludarabine. The 6-alkenylpurines, which are promising plant growth stimulators and 15-lipoxygenase inhibitors, exhibited only low toxicity.
|
Percent inhibition of [3H]-thymidine incorporation was determined in human chronic myelogenous leukemic K-562 cell line at 10 ug/mL after 48 hr
|
Homo sapiens
|
80.0
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Cytotoxic activity of 6-alkynyl- and 6-alkenylpurines.
Year : 2003
Volume : 13
Issue : 5
First Page : 877
Last Page : 880
Authors : Bråthe A, Gundersen LL, Nissen-Meyer J, Rise F, Spilsberg B.
Abstract : 6-Alkynyl- and 6-alkenylpurines have been screened for cytotoxic activity against a human chronic myelogenous leukemia cell line; K-562 cells using a [(3)H]-thymidine incorporation assay. Most alkynes displayed cytotoxicity comparable to, or better than, the known anticancer drugs 6-mercaptopurine and fludarabine. The 6-alkenylpurines, which are promising plant growth stimulators and 15-lipoxygenase inhibitors, exhibited only low toxicity.
|
Inhibitory concentration on multidrug-resistant L1210 leukemia cells.
|
Mus musculus
|
24.0
nM
|
|
Journal : J. Med. Chem.
Title : Additional nucleotide derivatives of mitosenes. Synthesis and activity against parental and multidrug resistant L1210 leukemia.
Year : 1991
Volume : 34
Issue : 7
First Page : 1947
Last Page : 1951
Authors : Iyengar BS, Dorr RT, Remers WA.
Abstract : Cytidine 5'-monophosphate and 5'-ara-CMP conjugates of 2,7-diaminomitosene, with the phosphate groups linked to C-1, were prepared by treating mitomycin C with the appropriate nucleotides. 5'-UMP conjugates were prepared from mitomycin A, 7 (M-83), and 8 (BMY-25282) by similar procedures. A conjugate could not be prepared from mitomycin C and 6-MPRP, but a sulfur-linked derivative was made with 6-MP ribonucleoside. The corresponding 1-hydroxy-2-aminomitosenes were prepared from the parent mitomycin analogues for structure-activity comparisons. All compounds were tested against L1210 murine leukemia in the MTT tetrazolium dye assay. In general, the conjugates were less potent than the parent mitomycins; however 5'-ara-CMP conjugate 14 derived from mitomycin C was more potent than the parent compound or any mitomycin tested except mitomycin A. It also was more potent than ara-C. This result establishes the value of this approach to prodrugs, at least in cell culture. Against a multi-drug-resistant L1210 cell line, all of the conjugates derived from mitomycin C were more potent than the parent compound. 6-Mercaptopurine ribonucleoside conjugate 15 was more active against the resistant cells than it was against the parental cell line.
|
Inhibitory concentration on parentral (sensitive) L1210 leukemia cells.
|
Mus musculus
|
20.0
nM
|
|
Journal : J. Med. Chem.
Title : Additional nucleotide derivatives of mitosenes. Synthesis and activity against parental and multidrug resistant L1210 leukemia.
Year : 1991
Volume : 34
Issue : 7
First Page : 1947
Last Page : 1951
Authors : Iyengar BS, Dorr RT, Remers WA.
Abstract : Cytidine 5'-monophosphate and 5'-ara-CMP conjugates of 2,7-diaminomitosene, with the phosphate groups linked to C-1, were prepared by treating mitomycin C with the appropriate nucleotides. 5'-UMP conjugates were prepared from mitomycin A, 7 (M-83), and 8 (BMY-25282) by similar procedures. A conjugate could not be prepared from mitomycin C and 6-MPRP, but a sulfur-linked derivative was made with 6-MP ribonucleoside. The corresponding 1-hydroxy-2-aminomitosenes were prepared from the parent mitomycin analogues for structure-activity comparisons. All compounds were tested against L1210 murine leukemia in the MTT tetrazolium dye assay. In general, the conjugates were less potent than the parent mitomycins; however 5'-ara-CMP conjugate 14 derived from mitomycin C was more potent than the parent compound or any mitomycin tested except mitomycin A. It also was more potent than ara-C. This result establishes the value of this approach to prodrugs, at least in cell culture. Against a multi-drug-resistant L1210 cell line, all of the conjugates derived from mitomycin C were more potent than the parent compound. 6-Mercaptopurine ribonucleoside conjugate 15 was more active against the resistant cells than it was against the parental cell line.
|
Percent inhibition of Ehrlich ascites carcinoma growth at 200 mg/kg per day
|
Mus musculus
|
99.6
%
|
|
Journal : J. Med. Chem.
Title : Synthesis and antitumor activity of a series of sulfone analogues of 1,4-naphthoquinone.
Year : 1981
Volume : 24
Issue : 7
First Page : 853
Last Page : 858
Authors : Holshouser MH, Loeffler LJ, Hall IH.
Abstract : A series of novel substituted thiochromones and thiochroman-4-ones was synthesized. Compounds were designed as analogues of naphthoquinone and as potential "bioreductive alkylating agents" and were tested for antitumor activity. The lead compound, 3-(chloromethyl)thiochromone 1,1-dioxide (4), inhibited Ehrlich ascites tumor growth by 100% in CF1 male mice at 10 (mg/kg)/day ip. Similarly, 18 of the 29 related compounds demonstrated good activity in this tumor screen. Few definitive structure-activity correlations were evident regarding the nature of the 3-substituent. However, the 2,3 double bond and a sulfone or sulfoxide were required for activity. Four of the compounds synthesized showed marginal but significant activity against P-388 lymphocytic leukemia.
|
Percentage inhibition as antitumor activity in carcinoma CF1 male mice.
|
Mus musculus
|
99.9
%
|
|
Journal : J. Med. Chem.
Title : Antitumor agents: diazomethyl ketone and chloromethyl ketone analogues prepared from N-tosyl amino acids.
Year : 1980
Volume : 23
Issue : 3
First Page : 275
Last Page : 278
Authors : Sajadi Z, Kashani M, Loeffler LJ, Hall IH.
Abstract : Diazomethyl ketone and chloromethyl ketone analogues prepared from N-tosyl amino acids have been synthesized and tested for antitumor activity in Ehrlich ascites carcinoma and P-388 lymphocytic leukemia screens in mice. The N-tosyl chloromethyl ketone analogues prepared from glycine, L-alanine, beta-alanine, L-valine, and 6-(N-tosyl-amino)caproic acid were the most potent antineoplastic agents in the Ehrlich ascites carcinoma screen. The N-tosyl diazomethyl ketone analogues synthesized from glycine, L-leucine, and L-proline were the most active of this series in the Ehrlich ascites screen, along with 5-keto-1-tosyl-2-(diazoacetyl)pyrrolidine and the diazomethyl ketone analogues prepared from 6-(N-tosylamino)caproic acid. In the P-388 lymphocytic leukemia screen, the N-tosyl chloromethyl ketone prepared from glycine and the compound 5-keto-1-tosyl-2-(diazoacetyl)pyrrolidine were the most active.
|
Antitumor activity in CF1 mice bearing Ehrlich ascites carcinoma measured as percentage inhibition at 50 mg/kg
|
Mus musculus
|
96.3
%
|
|
Journal : J. Med. Chem.
Title : Synthesis and antitumor evaluation of selected 5,6-disubstituted 1(2)H-indazole-4,7-diones.
Year : 1983
Volume : 26
Issue : 6
First Page : 876
Last Page : 884
Authors : Conway GA, Loeffler LJ, Hall IH.
Abstract : A series of novel aziridinyl-substituted 1(2)H-indazole-4,7-diones and related 1(2)H-indazole-4,7-diones was synthesized and tested against Ehrlich ascites carcinoma growth in male CF1 mice. Ten of the test compounds, including two aziridinyl-substituted 1(2)H-indazole-4,7-diones, were found to be significantly active (inhibition of tumor growth greater than 80%) in the Ehrlich ascites carcinoma screen. Several structure-activity relationships were indicated for antitumor activity in this screen. An aziridinyl-substituted derivative, 5-aziridinyl-6-chloro-1H-indazole-4,7-dione (8a), also exhibited significant activity against the growth of P-388 lymphocytic leukemia cells in male BDF1 mice (% T/C = 145; % T/C greater than 125 is considered significant).
|
Antiproliferative activity against human MT4 cells by MTT assay
|
Homo sapiens
|
100.0
nM
|
|
Journal : Eur. J. Med. Chem.
Title : Synthesis and antiproliferative properties of N3/8-disubstituted 3,8-diazabicyclo[3.2.1]octane analogues of 3,8-bis[2-(3,4,5-trimethoxyphenyl)pyridin-4-yl]methyl-piperazine.
Year : 2007
Volume : 42
Issue : 3
First Page : 293
Last Page : 306
Authors : Filosa R, Peduto A, de Caprariis P, Saturnino C, Festa M, Petrella A, Pau A, Pinna GA, La Colla P, Busonera B, Loddo R.
Abstract : A series of novel N(3/8)-disubstituted-3,8-diazabicyclo[3.2.1]octanes in order to improve the in vitro activity of the prototype 3,8-bis[2-(3,4,5-trimethoxyphenyl)pyridyl-4-yl)methylpiperazine (1) were synthesized and evaluated by assays of growth inhibition against several tumor cell lines. Compounds 2a,b,f and m demonstrated not only growth-inhibitory activities against leukemia cancer cells, but also fairly good activities against the growth of certain solid tumors. Among them, 2a is the most potent one with IC(50) values in the low micromolar range. Moreover, compound 2a has been selected for in vitro testing on MCF-7 cell to evaluate the mode of action of this lead compound.
|
Cytotoxicity against human KB cells after 72 hrs by MTT assay
|
Homo sapiens
|
0.55
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Bistramides A, B, C, D, and K: a new class of bioactive cyclic polyethers from Lissoclinum bistratum.
Year : 1994
Volume : 57
Issue : 10
First Page : 1336
Last Page : 1345
Authors : Biard JF, Roussakis C, Kornprobst JM, Gouiffes-Barbin D, Verbist JF, Cotelle P, Foster MP, Ireland CM, Debitus C.
Abstract : The isolation and characterization is described of four novel cyclic polyethers, bistramides B [2], C [3], D [4], and K [5], which are closely related to the previously reported bistramide A [1] from the New Caledonian urochordata Lissoclinum bistratum. The structures of these metabolites were defined by spectroscopic methods. The four compounds exhibited in vitro cytotoxicity toward six tumor cell lines, including the human non-small cell lung carcinoma (NSCLC-N6) line. Cytofluorimetric analysis with bistramide K showed a complete block of NSCLC-N6 cells in the G1 phase. Bistramide D and particularly bistramide K are less toxic than bistramides A, B, and C and are thereby effective in vivo against NSCLC-N6.
|
Cytotoxicity against mouse P388 cells after 72 hrs by MTT assay
|
Mus musculus
|
0.7
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Bistramides A, B, C, D, and K: a new class of bioactive cyclic polyethers from Lissoclinum bistratum.
Year : 1994
Volume : 57
Issue : 10
First Page : 1336
Last Page : 1345
Authors : Biard JF, Roussakis C, Kornprobst JM, Gouiffes-Barbin D, Verbist JF, Cotelle P, Foster MP, Ireland CM, Debitus C.
Abstract : The isolation and characterization is described of four novel cyclic polyethers, bistramides B [2], C [3], D [4], and K [5], which are closely related to the previously reported bistramide A [1] from the New Caledonian urochordata Lissoclinum bistratum. The structures of these metabolites were defined by spectroscopic methods. The four compounds exhibited in vitro cytotoxicity toward six tumor cell lines, including the human non-small cell lung carcinoma (NSCLC-N6) line. Cytofluorimetric analysis with bistramide K showed a complete block of NSCLC-N6 cells in the G1 phase. Bistramide D and particularly bistramide K are less toxic than bistramides A, B, and C and are thereby effective in vivo against NSCLC-N6.
|
Cytotoxicity against mouse doxorubicin resistant P388 cells after 72 hrs by MTT assay
|
Mus musculus
|
0.26
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Bistramides A, B, C, D, and K: a new class of bioactive cyclic polyethers from Lissoclinum bistratum.
Year : 1994
Volume : 57
Issue : 10
First Page : 1336
Last Page : 1345
Authors : Biard JF, Roussakis C, Kornprobst JM, Gouiffes-Barbin D, Verbist JF, Cotelle P, Foster MP, Ireland CM, Debitus C.
Abstract : The isolation and characterization is described of four novel cyclic polyethers, bistramides B [2], C [3], D [4], and K [5], which are closely related to the previously reported bistramide A [1] from the New Caledonian urochordata Lissoclinum bistratum. The structures of these metabolites were defined by spectroscopic methods. The four compounds exhibited in vitro cytotoxicity toward six tumor cell lines, including the human non-small cell lung carcinoma (NSCLC-N6) line. Cytofluorimetric analysis with bistramide K showed a complete block of NSCLC-N6 cells in the G1 phase. Bistramide D and particularly bistramide K are less toxic than bistramides A, B, and C and are thereby effective in vivo against NSCLC-N6.
|
Cytotoxicity against mouse B16 cells after 72 hrs by MTT assay
|
Mus musculus
|
0.8
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Bistramides A, B, C, D, and K: a new class of bioactive cyclic polyethers from Lissoclinum bistratum.
Year : 1994
Volume : 57
Issue : 10
First Page : 1336
Last Page : 1345
Authors : Biard JF, Roussakis C, Kornprobst JM, Gouiffes-Barbin D, Verbist JF, Cotelle P, Foster MP, Ireland CM, Debitus C.
Abstract : The isolation and characterization is described of four novel cyclic polyethers, bistramides B [2], C [3], D [4], and K [5], which are closely related to the previously reported bistramide A [1] from the New Caledonian urochordata Lissoclinum bistratum. The structures of these metabolites were defined by spectroscopic methods. The four compounds exhibited in vitro cytotoxicity toward six tumor cell lines, including the human non-small cell lung carcinoma (NSCLC-N6) line. Cytofluorimetric analysis with bistramide K showed a complete block of NSCLC-N6 cells in the G1 phase. Bistramide D and particularly bistramide K are less toxic than bistramides A, B, and C and are thereby effective in vivo against NSCLC-N6.
|
Cytotoxicity against human HT-29 cells after 72 hrs by MTT assay
|
Homo sapiens
|
0.87
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Bistramides A, B, C, D, and K: a new class of bioactive cyclic polyethers from Lissoclinum bistratum.
Year : 1994
Volume : 57
Issue : 10
First Page : 1336
Last Page : 1345
Authors : Biard JF, Roussakis C, Kornprobst JM, Gouiffes-Barbin D, Verbist JF, Cotelle P, Foster MP, Ireland CM, Debitus C.
Abstract : The isolation and characterization is described of four novel cyclic polyethers, bistramides B [2], C [3], D [4], and K [5], which are closely related to the previously reported bistramide A [1] from the New Caledonian urochordata Lissoclinum bistratum. The structures of these metabolites were defined by spectroscopic methods. The four compounds exhibited in vitro cytotoxicity toward six tumor cell lines, including the human non-small cell lung carcinoma (NSCLC-N6) line. Cytofluorimetric analysis with bistramide K showed a complete block of NSCLC-N6 cells in the G1 phase. Bistramide D and particularly bistramide K are less toxic than bistramides A, B, and C and are thereby effective in vivo against NSCLC-N6.
|
Cytotoxicity against human NSCLC-N6 cells after 72 hrs by MTT assay
|
Homo sapiens
|
0.79
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Bistramides A, B, C, D, and K: a new class of bioactive cyclic polyethers from Lissoclinum bistratum.
Year : 1994
Volume : 57
Issue : 10
First Page : 1336
Last Page : 1345
Authors : Biard JF, Roussakis C, Kornprobst JM, Gouiffes-Barbin D, Verbist JF, Cotelle P, Foster MP, Ireland CM, Debitus C.
Abstract : The isolation and characterization is described of four novel cyclic polyethers, bistramides B [2], C [3], D [4], and K [5], which are closely related to the previously reported bistramide A [1] from the New Caledonian urochordata Lissoclinum bistratum. The structures of these metabolites were defined by spectroscopic methods. The four compounds exhibited in vitro cytotoxicity toward six tumor cell lines, including the human non-small cell lung carcinoma (NSCLC-N6) line. Cytofluorimetric analysis with bistramide K showed a complete block of NSCLC-N6 cells in the G1 phase. Bistramide D and particularly bistramide K are less toxic than bistramides A, B, and C and are thereby effective in vivo against NSCLC-N6.
|
In vivo antineoplastic activity against mouse Ehrlich ascite carcinoma cells xenografted in CF1 mouse assessed as inhibition of tumor growth at 0.5 mg/kg/day after 9 days relative to control
|
Mus musculus
|
99.9
%
|
|
Journal : J. Nat. Prod.
Title : Hypolipidemic, anti-inflammatory, and antineoplastic activity and cytotoxicity of flavonolignans isolated from Hydnocarpus wightiana seeds.
Year : 1991
Volume : 54
Issue : 5
First Page : 1298
Last Page : 1302
Authors : Sharma DK, Hall IH.
Abstract : Flavonolignans isolated from Hydnocarpus wightiana seeds, namely hydnowightin, hydnocarpin, and neohydnocarpin, demonstrated potent hypolipidemic activity in mice, lowering both serum cholesterol and triglyceride levels at 8 mg/kg/day ip. Hydnowightin demonstrated the best lipid-lowering effect of the three compounds. Good anti-inflammatory and antineoplastic activity was demonstrated by hydnocarpin in mice in vivo. The other two derivatives were not as active in these screens. Cytotoxicity against the growth of murine and human tissue cultured cells was shown. All three compounds were moderately active against murine L-1210 leukemia growth. All three compounds demonstrated good activity against the growth of human KB nasopharynx, colon adenocarcinoma, osteosarcoma, and HeLa-S3 uterine growth. Hydnocarpin was the only compound of the three which was active against glioma growth. Hydnocarpin and neohydnocarpin demonstrated significant activity against Tmolt3 leukemia cell growth.
|
Cytotoxicity against human IGR-1 cells after 24 hrs by MTT assay
|
Homo sapiens
|
51.7
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Porrigenins A and B, novel cytotoxic and antiproliferative sapogenins isolated from Allium porrum.
Year : 1997
Volume : 60
Issue : 10
First Page : 1003
Last Page : 1007
Authors : Carotenuto A, Fattorusso E, Lanzotti V, Magno S, De Feo V, Carnuccio R, D'Acquisto F.
Abstract : Four new sapogenins, porrigenins A (2a) and B (3a), identified as (25R)-5 alpha-spirostan-2 beta,3 beta,6 beta-triol and (25R)-2-oxo-5 alpha-spirostan-3 beta,6 beta-diol, respectively, and neoporrigenins A (2b) and B (3b) were also isolated from Allium porrum. In addition, the known agigenin (1a) and its 25S epimer, neoagigenin (1b), were also identified. Their structure elucidation was provided by comprehensive spectroscopic analyses. Compounds 1a, 2a, and 3a exhibited cytotoxicity and high antiproliferative activity on four different tumor cell lines in vitro.
|
Antiproliferative activity against human IGR-1 cells after 48 hrs by MTT assay
|
Homo sapiens
|
12.3
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Porrigenins A and B, novel cytotoxic and antiproliferative sapogenins isolated from Allium porrum.
Year : 1997
Volume : 60
Issue : 10
First Page : 1003
Last Page : 1007
Authors : Carotenuto A, Fattorusso E, Lanzotti V, Magno S, De Feo V, Carnuccio R, D'Acquisto F.
Abstract : Four new sapogenins, porrigenins A (2a) and B (3a), identified as (25R)-5 alpha-spirostan-2 beta,3 beta,6 beta-triol and (25R)-2-oxo-5 alpha-spirostan-3 beta,6 beta-diol, respectively, and neoporrigenins A (2b) and B (3b) were also isolated from Allium porrum. In addition, the known agigenin (1a) and its 25S epimer, neoagigenin (1b), were also identified. Their structure elucidation was provided by comprehensive spectroscopic analyses. Compounds 1a, 2a, and 3a exhibited cytotoxicity and high antiproliferative activity on four different tumor cell lines in vitro.
|
Antiproliferative activity against human IGR-1 cells after 72 hrs by MTT assay
|
Homo sapiens
|
1.1
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Porrigenins A and B, novel cytotoxic and antiproliferative sapogenins isolated from Allium porrum.
Year : 1997
Volume : 60
Issue : 10
First Page : 1003
Last Page : 1007
Authors : Carotenuto A, Fattorusso E, Lanzotti V, Magno S, De Feo V, Carnuccio R, D'Acquisto F.
Abstract : Four new sapogenins, porrigenins A (2a) and B (3a), identified as (25R)-5 alpha-spirostan-2 beta,3 beta,6 beta-triol and (25R)-2-oxo-5 alpha-spirostan-3 beta,6 beta-diol, respectively, and neoporrigenins A (2b) and B (3b) were also isolated from Allium porrum. In addition, the known agigenin (1a) and its 25S epimer, neoagigenin (1b), were also identified. Their structure elucidation was provided by comprehensive spectroscopic analyses. Compounds 1a, 2a, and 3a exhibited cytotoxicity and high antiproliferative activity on four different tumor cell lines in vitro.
|
Cytotoxicity against mouse J774 cells after 24 hrs by MTT assay
|
Mus musculus
|
61.0
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Porrigenins A and B, novel cytotoxic and antiproliferative sapogenins isolated from Allium porrum.
Year : 1997
Volume : 60
Issue : 10
First Page : 1003
Last Page : 1007
Authors : Carotenuto A, Fattorusso E, Lanzotti V, Magno S, De Feo V, Carnuccio R, D'Acquisto F.
Abstract : Four new sapogenins, porrigenins A (2a) and B (3a), identified as (25R)-5 alpha-spirostan-2 beta,3 beta,6 beta-triol and (25R)-2-oxo-5 alpha-spirostan-3 beta,6 beta-diol, respectively, and neoporrigenins A (2b) and B (3b) were also isolated from Allium porrum. In addition, the known agigenin (1a) and its 25S epimer, neoagigenin (1b), were also identified. Their structure elucidation was provided by comprehensive spectroscopic analyses. Compounds 1a, 2a, and 3a exhibited cytotoxicity and high antiproliferative activity on four different tumor cell lines in vitro.
|
Antiproliferative activity against mouse J774 cells after 48 hrs by MTT assay
|
Mus musculus
|
3.6
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Porrigenins A and B, novel cytotoxic and antiproliferative sapogenins isolated from Allium porrum.
Year : 1997
Volume : 60
Issue : 10
First Page : 1003
Last Page : 1007
Authors : Carotenuto A, Fattorusso E, Lanzotti V, Magno S, De Feo V, Carnuccio R, D'Acquisto F.
Abstract : Four new sapogenins, porrigenins A (2a) and B (3a), identified as (25R)-5 alpha-spirostan-2 beta,3 beta,6 beta-triol and (25R)-2-oxo-5 alpha-spirostan-3 beta,6 beta-diol, respectively, and neoporrigenins A (2b) and B (3b) were also isolated from Allium porrum. In addition, the known agigenin (1a) and its 25S epimer, neoagigenin (1b), were also identified. Their structure elucidation was provided by comprehensive spectroscopic analyses. Compounds 1a, 2a, and 3a exhibited cytotoxicity and high antiproliferative activity on four different tumor cell lines in vitro.
|
Antiproliferative activity against mouse J774 cells after 72 hrs by MTT assay
|
Mus musculus
|
0.5
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Porrigenins A and B, novel cytotoxic and antiproliferative sapogenins isolated from Allium porrum.
Year : 1997
Volume : 60
Issue : 10
First Page : 1003
Last Page : 1007
Authors : Carotenuto A, Fattorusso E, Lanzotti V, Magno S, De Feo V, Carnuccio R, D'Acquisto F.
Abstract : Four new sapogenins, porrigenins A (2a) and B (3a), identified as (25R)-5 alpha-spirostan-2 beta,3 beta,6 beta-triol and (25R)-2-oxo-5 alpha-spirostan-3 beta,6 beta-diol, respectively, and neoporrigenins A (2b) and B (3b) were also isolated from Allium porrum. In addition, the known agigenin (1a) and its 25S epimer, neoagigenin (1b), were also identified. Their structure elucidation was provided by comprehensive spectroscopic analyses. Compounds 1a, 2a, and 3a exhibited cytotoxicity and high antiproliferative activity on four different tumor cell lines in vitro.
|
Cytotoxicity against mouse WEHI164 cells after 24 hrs by MTT assay
|
Mus musculus
|
83.0
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Porrigenins A and B, novel cytotoxic and antiproliferative sapogenins isolated from Allium porrum.
Year : 1997
Volume : 60
Issue : 10
First Page : 1003
Last Page : 1007
Authors : Carotenuto A, Fattorusso E, Lanzotti V, Magno S, De Feo V, Carnuccio R, D'Acquisto F.
Abstract : Four new sapogenins, porrigenins A (2a) and B (3a), identified as (25R)-5 alpha-spirostan-2 beta,3 beta,6 beta-triol and (25R)-2-oxo-5 alpha-spirostan-3 beta,6 beta-diol, respectively, and neoporrigenins A (2b) and B (3b) were also isolated from Allium porrum. In addition, the known agigenin (1a) and its 25S epimer, neoagigenin (1b), were also identified. Their structure elucidation was provided by comprehensive spectroscopic analyses. Compounds 1a, 2a, and 3a exhibited cytotoxicity and high antiproliferative activity on four different tumor cell lines in vitro.
|
Antiproliferative activity against mouse WEHI164 cells after 48 hrs by MTT assay
|
Mus musculus
|
42.0
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Porrigenins A and B, novel cytotoxic and antiproliferative sapogenins isolated from Allium porrum.
Year : 1997
Volume : 60
Issue : 10
First Page : 1003
Last Page : 1007
Authors : Carotenuto A, Fattorusso E, Lanzotti V, Magno S, De Feo V, Carnuccio R, D'Acquisto F.
Abstract : Four new sapogenins, porrigenins A (2a) and B (3a), identified as (25R)-5 alpha-spirostan-2 beta,3 beta,6 beta-triol and (25R)-2-oxo-5 alpha-spirostan-3 beta,6 beta-diol, respectively, and neoporrigenins A (2b) and B (3b) were also isolated from Allium porrum. In addition, the known agigenin (1a) and its 25S epimer, neoagigenin (1b), were also identified. Their structure elucidation was provided by comprehensive spectroscopic analyses. Compounds 1a, 2a, and 3a exhibited cytotoxicity and high antiproliferative activity on four different tumor cell lines in vitro.
|
Antiproliferative activity against mouse WEHI164 cells after 72 hrs by MTT assay
|
Mus musculus
|
2.7
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Porrigenins A and B, novel cytotoxic and antiproliferative sapogenins isolated from Allium porrum.
Year : 1997
Volume : 60
Issue : 10
First Page : 1003
Last Page : 1007
Authors : Carotenuto A, Fattorusso E, Lanzotti V, Magno S, De Feo V, Carnuccio R, D'Acquisto F.
Abstract : Four new sapogenins, porrigenins A (2a) and B (3a), identified as (25R)-5 alpha-spirostan-2 beta,3 beta,6 beta-triol and (25R)-2-oxo-5 alpha-spirostan-3 beta,6 beta-diol, respectively, and neoporrigenins A (2b) and B (3b) were also isolated from Allium porrum. In addition, the known agigenin (1a) and its 25S epimer, neoagigenin (1b), were also identified. Their structure elucidation was provided by comprehensive spectroscopic analyses. Compounds 1a, 2a, and 3a exhibited cytotoxicity and high antiproliferative activity on four different tumor cell lines in vitro.
|
Cytotoxicity against mouse P388 cells after 24 hrs by MTT assay
|
Mus musculus
|
37.0
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Porrigenins A and B, novel cytotoxic and antiproliferative sapogenins isolated from Allium porrum.
Year : 1997
Volume : 60
Issue : 10
First Page : 1003
Last Page : 1007
Authors : Carotenuto A, Fattorusso E, Lanzotti V, Magno S, De Feo V, Carnuccio R, D'Acquisto F.
Abstract : Four new sapogenins, porrigenins A (2a) and B (3a), identified as (25R)-5 alpha-spirostan-2 beta,3 beta,6 beta-triol and (25R)-2-oxo-5 alpha-spirostan-3 beta,6 beta-diol, respectively, and neoporrigenins A (2b) and B (3b) were also isolated from Allium porrum. In addition, the known agigenin (1a) and its 25S epimer, neoagigenin (1b), were also identified. Their structure elucidation was provided by comprehensive spectroscopic analyses. Compounds 1a, 2a, and 3a exhibited cytotoxicity and high antiproliferative activity on four different tumor cell lines in vitro.
|
Antiproliferative activity against mouse P388 cells after 48 hrs by MTT assay
|
Mus musculus
|
2.1
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Porrigenins A and B, novel cytotoxic and antiproliferative sapogenins isolated from Allium porrum.
Year : 1997
Volume : 60
Issue : 10
First Page : 1003
Last Page : 1007
Authors : Carotenuto A, Fattorusso E, Lanzotti V, Magno S, De Feo V, Carnuccio R, D'Acquisto F.
Abstract : Four new sapogenins, porrigenins A (2a) and B (3a), identified as (25R)-5 alpha-spirostan-2 beta,3 beta,6 beta-triol and (25R)-2-oxo-5 alpha-spirostan-3 beta,6 beta-diol, respectively, and neoporrigenins A (2b) and B (3b) were also isolated from Allium porrum. In addition, the known agigenin (1a) and its 25S epimer, neoagigenin (1b), were also identified. Their structure elucidation was provided by comprehensive spectroscopic analyses. Compounds 1a, 2a, and 3a exhibited cytotoxicity and high antiproliferative activity on four different tumor cell lines in vitro.
|
Antiproliferative activity against mouse P388 cells after 72 hrs by MTT assay
|
Mus musculus
|
0.3
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Porrigenins A and B, novel cytotoxic and antiproliferative sapogenins isolated from Allium porrum.
Year : 1997
Volume : 60
Issue : 10
First Page : 1003
Last Page : 1007
Authors : Carotenuto A, Fattorusso E, Lanzotti V, Magno S, De Feo V, Carnuccio R, D'Acquisto F.
Abstract : Four new sapogenins, porrigenins A (2a) and B (3a), identified as (25R)-5 alpha-spirostan-2 beta,3 beta,6 beta-triol and (25R)-2-oxo-5 alpha-spirostan-3 beta,6 beta-diol, respectively, and neoporrigenins A (2b) and B (3b) were also isolated from Allium porrum. In addition, the known agigenin (1a) and its 25S epimer, neoagigenin (1b), were also identified. Their structure elucidation was provided by comprehensive spectroscopic analyses. Compounds 1a, 2a, and 3a exhibited cytotoxicity and high antiproliferative activity on four different tumor cell lines in vitro.
|
Antiproliferative activity against mouse WEHI164 cells assessed as cell viability after 96 hrs by MTT assay
|
Mus musculus
|
1.3
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : New bioactive sulfated metabolites from the Mediterranean tunicate Sidnyum turbinatum.
Year : 2001
Volume : 64
Issue : 2
First Page : 219
Last Page : 221
Authors : Aiello A, Carbonelli S, Fattorusso E, Iuvone T, Menna M.
Abstract : In addition to the known sodium 3,7,11,15-tetramethylhexadeca-1,19-diyl sulfate (4), the BuOH extract of the Mediterranean tunicate Sidnyum turbinatum was shown to contain four new metabolites: 1-heptadecanyl sulfate (1), 1-octadecanyl sulfate (2), sodium (2S)-2,6,10,14-tetramethylpentadeca-1,18-diyl sulfate (3), and 1-hexyl sulfate (5). Their structures were determined by spectroscopic and chemical methods. Compounds 1-5 exhibited in vitro antiproliferative activity estimated on the WEHI 164 cell line.
|
Antiproliferative activity against mouse J774.A1 cells after 3 days by MTT conversion assay
|
Mus musculus
|
3.0
nM
|
|
Journal : J. Nat. Prod.
Title : Pregnane glycosides from Leptadenia pyrotechnica.
Year : 2006
Volume : 69
Issue : 4
First Page : 625
Last Page : 635
Authors : Cioffi G, Sanogo R, Vassallo A, Dal Piaz F, Autore G, Marzocco S, De Tommasi N.
Abstract : The whole plant of Leptadenia pyrotechnica afforded 18 new pregnane glycosides (1-18) with sarcostin, 11-hydroxysarcostin, and deacetylmetaplexigenin as the aglycon moieties and acetyl, benzoyl, cinnamoyl, p-coumaroyl, and nicotinoyl ester moieties linked at C-12 and/or C-20 of the aglycon and hexopyranose, 6-deoxy-3-O-methylhexopyranose, and 2,6-dideoxy-3-O-methylhexopyranose sugars linked at C-3 of their aglycon. The structures of these compounds were elucidated by spectroscopic data interpretation and from chemical evidence. The antiproliferative activity of all compounds was evaluated using three continuous murine and human culture cell lines, J774.A1, HEK-293, and WEHI-164. Compounds having deacethylmetaplexigenin as aglycon and a cinnamoyl ester moiety linked at C-12 were the most active constituents.
|
Antiproliferative activity against HEK293 cells after 3 days by MTT conversion assay
|
Homo sapiens
|
7.0
nM
|
|
Journal : J. Nat. Prod.
Title : Pregnane glycosides from Leptadenia pyrotechnica.
Year : 2006
Volume : 69
Issue : 4
First Page : 625
Last Page : 635
Authors : Cioffi G, Sanogo R, Vassallo A, Dal Piaz F, Autore G, Marzocco S, De Tommasi N.
Abstract : The whole plant of Leptadenia pyrotechnica afforded 18 new pregnane glycosides (1-18) with sarcostin, 11-hydroxysarcostin, and deacetylmetaplexigenin as the aglycon moieties and acetyl, benzoyl, cinnamoyl, p-coumaroyl, and nicotinoyl ester moieties linked at C-12 and/or C-20 of the aglycon and hexopyranose, 6-deoxy-3-O-methylhexopyranose, and 2,6-dideoxy-3-O-methylhexopyranose sugars linked at C-3 of their aglycon. The structures of these compounds were elucidated by spectroscopic data interpretation and from chemical evidence. The antiproliferative activity of all compounds was evaluated using three continuous murine and human culture cell lines, J774.A1, HEK-293, and WEHI-164. Compounds having deacethylmetaplexigenin as aglycon and a cinnamoyl ester moiety linked at C-12 were the most active constituents.
|
Antiproliferative activity against mouse WEHI164 cells after 3 days by MTT conversion assay
|
Mus musculus
|
15.0
nM
|
|
Journal : J. Nat. Prod.
Title : Pregnane glycosides from Leptadenia pyrotechnica.
Year : 2006
Volume : 69
Issue : 4
First Page : 625
Last Page : 635
Authors : Cioffi G, Sanogo R, Vassallo A, Dal Piaz F, Autore G, Marzocco S, De Tommasi N.
Abstract : The whole plant of Leptadenia pyrotechnica afforded 18 new pregnane glycosides (1-18) with sarcostin, 11-hydroxysarcostin, and deacetylmetaplexigenin as the aglycon moieties and acetyl, benzoyl, cinnamoyl, p-coumaroyl, and nicotinoyl ester moieties linked at C-12 and/or C-20 of the aglycon and hexopyranose, 6-deoxy-3-O-methylhexopyranose, and 2,6-dideoxy-3-O-methylhexopyranose sugars linked at C-3 of their aglycon. The structures of these compounds were elucidated by spectroscopic data interpretation and from chemical evidence. The antiproliferative activity of all compounds was evaluated using three continuous murine and human culture cell lines, J774.A1, HEK-293, and WEHI-164. Compounds having deacethylmetaplexigenin as aglycon and a cinnamoyl ester moiety linked at C-12 were the most active constituents.
|
Cytotoxicity against mouse WEHI164 cells assessed as cell viability after 96 hrs by MTT assay
|
Mus musculus
|
1.3
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Novel bioactive sulfated alkene and alkanes from the mediterranean ascidian Halocynthia papillosa.
Year : 2000
Volume : 63
Issue : 11
First Page : 1590
Last Page : 1592
Authors : Aiello A, Carbonelli S, Esposito G, Fattorusso E, Iuvone T, Menna M.
Abstract : Three sulfated alkene and alkanes-(R)-2,6-dimethylheptyl sulfate (1), 6-methylheptyl sulfate (2a), and (E)-5-octenyl sulfate (3a)-with cytotoxic activity in vitro, have been isolated from the Mediterranean ascidian Halocynthia papillosa. The structures of the new compounds 2a and 3a have been elucidated by spectroscopic analysis.
|
Cytotoxicity against rat C6 cells assessed as cell viability after 96 hrs by MTT assay
|
Rattus norvegicus
|
30.2
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Novel bioactive sulfated alkene and alkanes from the mediterranean ascidian Halocynthia papillosa.
Year : 2000
Volume : 63
Issue : 11
First Page : 1590
Last Page : 1592
Authors : Aiello A, Carbonelli S, Esposito G, Fattorusso E, Iuvone T, Menna M.
Abstract : Three sulfated alkene and alkanes-(R)-2,6-dimethylheptyl sulfate (1), 6-methylheptyl sulfate (2a), and (E)-5-octenyl sulfate (3a)-with cytotoxic activity in vitro, have been isolated from the Mediterranean ascidian Halocynthia papillosa. The structures of the new compounds 2a and 3a have been elucidated by spectroscopic analysis.
|
Antiproliferative activity against mouse J774 cells assessed as reduction of cell growth after 72 hrs by MTT method
|
Mus musculus
|
3.0
nM
|
|
Journal : J. Nat. Prod.
Title : Antiproliferative triterpene saponins from Trevesia palmata.
Year : 2000
Volume : 63
Issue : 3
First Page : 308
Last Page : 314
Authors : De Tommasi N, Autore G, Bellino A, Pinto A, Pizza C, Sorrentino R, Venturella P.
Abstract : During the course of a study of plants of the family Araliaceae, antiproliferative activity was demonstrated by the crude saponin fraction of Trevesia palmata. After chromatographic purification, six new bisdesmosidic saponins (1-6), along with two known triterpenoid saponins, (7 and 8), were isolated. The structures of 1-6 were determined by (1)H-(1)H correlation spectroscopy (COSY-DQF, 1D TOCSY, 2D HOHAHA, 1D ROESY) and (1)H-(13)C (HSQC, HMBC) spectroscopy. The antiproliferative activity of compounds 1-8 and of their prosapogenins (2a-7a) prepared by alkaline hydrolysis, was evaluated using three continuous culture cell lines.
|
Antiproliferative activity against HEK293 cells assessed as reduction of cell growth after 72 hrs by MTT method
|
Homo sapiens
|
7.0
nM
|
|
Journal : J. Nat. Prod.
Title : Antiproliferative triterpene saponins from Trevesia palmata.
Year : 2000
Volume : 63
Issue : 3
First Page : 308
Last Page : 314
Authors : De Tommasi N, Autore G, Bellino A, Pinto A, Pizza C, Sorrentino R, Venturella P.
Abstract : During the course of a study of plants of the family Araliaceae, antiproliferative activity was demonstrated by the crude saponin fraction of Trevesia palmata. After chromatographic purification, six new bisdesmosidic saponins (1-6), along with two known triterpenoid saponins, (7 and 8), were isolated. The structures of 1-6 were determined by (1)H-(1)H correlation spectroscopy (COSY-DQF, 1D TOCSY, 2D HOHAHA, 1D ROESY) and (1)H-(13)C (HSQC, HMBC) spectroscopy. The antiproliferative activity of compounds 1-8 and of their prosapogenins (2a-7a) prepared by alkaline hydrolysis, was evaluated using three continuous culture cell lines.
|
Antiproliferative activity against mouse WEHI164 cells assessed as reduction of cell growth after 72 hrs by MTT method
|
Mus musculus
|
17.0
nM
|
|
Journal : J. Nat. Prod.
Title : Antiproliferative triterpene saponins from Trevesia palmata.
Year : 2000
Volume : 63
Issue : 3
First Page : 308
Last Page : 314
Authors : De Tommasi N, Autore G, Bellino A, Pinto A, Pizza C, Sorrentino R, Venturella P.
Abstract : During the course of a study of plants of the family Araliaceae, antiproliferative activity was demonstrated by the crude saponin fraction of Trevesia palmata. After chromatographic purification, six new bisdesmosidic saponins (1-6), along with two known triterpenoid saponins, (7 and 8), were isolated. The structures of 1-6 were determined by (1)H-(1)H correlation spectroscopy (COSY-DQF, 1D TOCSY, 2D HOHAHA, 1D ROESY) and (1)H-(13)C (HSQC, HMBC) spectroscopy. The antiproliferative activity of compounds 1-8 and of their prosapogenins (2a-7a) prepared by alkaline hydrolysis, was evaluated using three continuous culture cell lines.
|
Antiproliferative activity against mouse J774A1 cells after 72 hrs by MTT conversion assay
|
Mus musculus
|
3.0
nM
|
|
Journal : J. Nat. Prod.
Title : Antiproliferative triterpene saponins from Entada africana.
Year : 2006
Volume : 69
Issue : 9
First Page : 1323
Last Page : 1329
Authors : Cioffi G, Dal Piaz F, De Caprariis P, Sanogo R, Marzocco S, Autore G, De Tommasi N.
Abstract : Nine new ester saponins (1-9) were isolated from the roots of Entada africana. Their structures were elucidated by 1D and 2D NMR experiments including 1D and 2D TOCSY, DQF-COSY, HSQC, and HMBC spectroscopy, as well as ESIMS analysis, and chemical methods. The aglycon moieties were found to be echinocystic acid for compounds 1, 2, 4-6, 8, and 9 and acacic acid for 3 and 7. All isolated compounds were tested for their antiproliferative activity against the J774.A1, HEK-293, and WEHI-164 cell lines. Moderate to high cytotoxic potency was found for almost all compounds tested.
|
Antiproliferative activity against HEK293 cells after 72 hrs by MTT conversion assay
|
Homo sapiens
|
7.0
nM
|
|
Journal : J. Nat. Prod.
Title : Antiproliferative triterpene saponins from Entada africana.
Year : 2006
Volume : 69
Issue : 9
First Page : 1323
Last Page : 1329
Authors : Cioffi G, Dal Piaz F, De Caprariis P, Sanogo R, Marzocco S, Autore G, De Tommasi N.
Abstract : Nine new ester saponins (1-9) were isolated from the roots of Entada africana. Their structures were elucidated by 1D and 2D NMR experiments including 1D and 2D TOCSY, DQF-COSY, HSQC, and HMBC spectroscopy, as well as ESIMS analysis, and chemical methods. The aglycon moieties were found to be echinocystic acid for compounds 1, 2, 4-6, 8, and 9 and acacic acid for 3 and 7. All isolated compounds were tested for their antiproliferative activity against the J774.A1, HEK-293, and WEHI-164 cell lines. Moderate to high cytotoxic potency was found for almost all compounds tested.
|
Antiproliferative activity against mouse WEHI164 cells after 72 hrs by MTT conversion assay
|
Mus musculus
|
15.0
nM
|
|
Journal : J. Nat. Prod.
Title : Antiproliferative triterpene saponins from Entada africana.
Year : 2006
Volume : 69
Issue : 9
First Page : 1323
Last Page : 1329
Authors : Cioffi G, Dal Piaz F, De Caprariis P, Sanogo R, Marzocco S, Autore G, De Tommasi N.
Abstract : Nine new ester saponins (1-9) were isolated from the roots of Entada africana. Their structures were elucidated by 1D and 2D NMR experiments including 1D and 2D TOCSY, DQF-COSY, HSQC, and HMBC spectroscopy, as well as ESIMS analysis, and chemical methods. The aglycon moieties were found to be echinocystic acid for compounds 1, 2, 4-6, 8, and 9 and acacic acid for 3 and 7. All isolated compounds were tested for their antiproliferative activity against the J774.A1, HEK-293, and WEHI-164 cell lines. Moderate to high cytotoxic potency was found for almost all compounds tested.
|
Antiproliferative activity against mouse J774.A1 cells after 72 hrs by MTT conversion assay
|
Mus musculus
|
3.0
nM
|
|
Journal : J. Nat. Prod.
Title : Antiproliferative oleanane saponins from Meryta denhamii.
Year : 2008
Volume : 71
Issue : 6
First Page : 1000
Last Page : 1004
Authors : Cioffi G, Dal Piaz F, Vassallo A, Venturella F, De Caprariis P, De Simone F, De Tommasi N.
Abstract : Eight new oleanane saponins (1- 8) together with four know saponins (9-12) were isolated from the aerial parts of Meryta denhamii. Their structures were elucidated by 1D and 2D NMR experiments including 1D TOCSY, DQF-COSY, ROESY, HSQC, and HMBC spectroscopy, as well as ESIMS analysis. The antiproliferative activity of all compounds was evaluated using three murine and human cancer cell lines: J774.A1, HEK-293, and WEHI-164.
|
Antiproliferative activity against human HEK293 cells after 72 hrs by MTT conversion assay
|
Homo sapiens
|
7.0
nM
|
|
Journal : J. Nat. Prod.
Title : Antiproliferative oleanane saponins from Meryta denhamii.
Year : 2008
Volume : 71
Issue : 6
First Page : 1000
Last Page : 1004
Authors : Cioffi G, Dal Piaz F, Vassallo A, Venturella F, De Caprariis P, De Simone F, De Tommasi N.
Abstract : Eight new oleanane saponins (1- 8) together with four know saponins (9-12) were isolated from the aerial parts of Meryta denhamii. Their structures were elucidated by 1D and 2D NMR experiments including 1D TOCSY, DQF-COSY, ROESY, HSQC, and HMBC spectroscopy, as well as ESIMS analysis. The antiproliferative activity of all compounds was evaluated using three murine and human cancer cell lines: J774.A1, HEK-293, and WEHI-164.
|
Antiproliferative activity against mouse WEHI164 cells after 72 hrs by MTT conversion assay
|
Mus musculus
|
15.0
nM
|
|
Journal : J. Nat. Prod.
Title : Antiproliferative oleanane saponins from Meryta denhamii.
Year : 2008
Volume : 71
Issue : 6
First Page : 1000
Last Page : 1004
Authors : Cioffi G, Dal Piaz F, Vassallo A, Venturella F, De Caprariis P, De Simone F, De Tommasi N.
Abstract : Eight new oleanane saponins (1- 8) together with four know saponins (9-12) were isolated from the aerial parts of Meryta denhamii. Their structures were elucidated by 1D and 2D NMR experiments including 1D TOCSY, DQF-COSY, ROESY, HSQC, and HMBC spectroscopy, as well as ESIMS analysis. The antiproliferative activity of all compounds was evaluated using three murine and human cancer cell lines: J774.A1, HEK-293, and WEHI-164.
|
Inhibition of T cell mitogen-induced blastogenesis in human PBMC after 4 days
|
Homo sapiens
|
149.5
nM
|
|
Journal : Eur. J. Med. Chem.
Title : Novel derivatives of 6-mercaptopurine: synthesis, characterization and antiproliferative activities of S-allylthio-mercaptopurines.
Year : 2009
Volume : 44
Issue : 2
First Page : 541
Last Page : 550
Authors : Miron T, Arditti F, Konstantinovski L, Rabinkov A, Mirelman D, Berrebi A, Wilchek M.
Abstract : Biologically active S-allylthio derivatives of 6-mercaptopurine (6-MP) and 6-mercaptopurine riboside (6-MPR) were synthesized. The products, S-allylthio-6-mercaptopurine (SA-6MP) and S-allylthio-6-mercaptopurine riboside (SA-6MPR) were characterized. The antiproliferative activity of the new prodrugs was tested on human leukemia and monolayer cell lines, and compared to that of their parent reactants. The new prodrugs acted by a concentration-dependent mechanism. They inhibited cell proliferation and induced-apoptosis more efficiently than the parent molecules. Leukemia cell lines were more sensitive to the new prodrugs than monolayer cell lines. Higher hydrophobicity of the derivatives improves their penetration into cells, where upon reaction with glutathione, S-allylthioglutathione (GSSA) is formed, and 6-MP or 6-MPR is released for further processing.
|
Cytotoxicity against mouse WEHI164 cells by rapid colorimetric assay
|
Mus musculus
|
0.0025
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : 3-Alkylpyridinium alkaloids from the Pacific sponge Haliclona sp.
Year : 2009
Volume : 72
Issue : 2
First Page : 301
Last Page : 303
Authors : Casapullo A, Pinto OC, Marzocco S, Autore G, Riccio R.
Abstract : The analysis of the polar extracts of the Pacific sponge Haliclona sp. yielded new dimeric (1), trimeric (2), and polymeric 3-alkylpyridinium alkaloids. Their isolation and structural elucidation, based on NMR and MS data, are discussed in detail, along with their cytotoxic activity.
|
Cytotoxicity against HEK293 cells by rapid colorimetric assay
|
Homo sapiens
|
0.00071
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : 3-Alkylpyridinium alkaloids from the Pacific sponge Haliclona sp.
Year : 2009
Volume : 72
Issue : 2
First Page : 301
Last Page : 303
Authors : Casapullo A, Pinto OC, Marzocco S, Autore G, Riccio R.
Abstract : The analysis of the polar extracts of the Pacific sponge Haliclona sp. yielded new dimeric (1), trimeric (2), and polymeric 3-alkylpyridinium alkaloids. Their isolation and structural elucidation, based on NMR and MS data, are discussed in detail, along with their cytotoxic activity.
|
Cytotoxicity against mouse J774A1 cells by rapid colorimetric assay
|
Mus musculus
|
0.0051
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : 3-Alkylpyridinium alkaloids from the Pacific sponge Haliclona sp.
Year : 2009
Volume : 72
Issue : 2
First Page : 301
Last Page : 303
Authors : Casapullo A, Pinto OC, Marzocco S, Autore G, Riccio R.
Abstract : The analysis of the polar extracts of the Pacific sponge Haliclona sp. yielded new dimeric (1), trimeric (2), and polymeric 3-alkylpyridinium alkaloids. Their isolation and structural elucidation, based on NMR and MS data, are discussed in detail, along with their cytotoxic activity.
|
Antiproliferative activity against mouse J774A1 cells assessed as cell viability at 100 ug/ml after 72 hrs by MTT assay relative to LPS
|
Mus musculus
|
31.8
%
|
|
Journal : J. Nat. Prod.
Title : Phenylethanoid glycosides from Lantana fucata with in vitro anti-inflammatory activity.
Year : 2009
Volume : 72
Issue : 8
First Page : 1424
Last Page : 1428
Authors : Julião Lde S, Piccinelli AL, Marzocco S, Leitão SG, Lotti C, Autore G, Rastrelli L.
Abstract : A phytochemical analysis of Lantana fucata dried leaves led to the isolation of three new phenylethanoid glycosides, fucatosides A-C, along with parvifloroside A and six known methoxyflavones. Their structures were established by NMR and ESIMS experiments. In vitro assays showed that the alcoholic extract and fucatoside C have significant anti-inflammatory effects, inhibiting NO release in the LPS-induced J774.A1 murine macrophage cell line.
|
Antiproliferative activity against mouse J774A1 cells assessed as cell viability at 10 ug/ml after 72 hrs by MTT assay relative to LPS
|
Mus musculus
|
38.0
%
|
|
Journal : J. Nat. Prod.
Title : Phenylethanoid glycosides from Lantana fucata with in vitro anti-inflammatory activity.
Year : 2009
Volume : 72
Issue : 8
First Page : 1424
Last Page : 1428
Authors : Julião Lde S, Piccinelli AL, Marzocco S, Leitão SG, Lotti C, Autore G, Rastrelli L.
Abstract : A phytochemical analysis of Lantana fucata dried leaves led to the isolation of three new phenylethanoid glycosides, fucatosides A-C, along with parvifloroside A and six known methoxyflavones. Their structures were established by NMR and ESIMS experiments. In vitro assays showed that the alcoholic extract and fucatoside C have significant anti-inflammatory effects, inhibiting NO release in the LPS-induced J774.A1 murine macrophage cell line.
|
Antiproliferative activity against mouse J774A1 cells assessed as cell viability at 1 ug/ml after 72 hrs by MTT assay relative to LPS
|
Mus musculus
|
44.1
%
|
|
Journal : J. Nat. Prod.
Title : Phenylethanoid glycosides from Lantana fucata with in vitro anti-inflammatory activity.
Year : 2009
Volume : 72
Issue : 8
First Page : 1424
Last Page : 1428
Authors : Julião Lde S, Piccinelli AL, Marzocco S, Leitão SG, Lotti C, Autore G, Rastrelli L.
Abstract : A phytochemical analysis of Lantana fucata dried leaves led to the isolation of three new phenylethanoid glycosides, fucatosides A-C, along with parvifloroside A and six known methoxyflavones. Their structures were established by NMR and ESIMS experiments. In vitro assays showed that the alcoholic extract and fucatoside C have significant anti-inflammatory effects, inhibiting NO release in the LPS-induced J774.A1 murine macrophage cell line.
|
Inhibition of sodium fluorescein uptake in OATP1B1-transfected CHO cells at an equimolar substrate-inhibitor concentration of 10 uM
|
Cricetulus griseus
|
107.78
%
|
|
Journal : Mol. Pharmacol.
Title : Structure-based identification of OATP1B1/3 inhibitors.
Year : 2013
Volume : 83
Issue : 6
First Page : 1257
Last Page : 1267
Authors : De Bruyn T, van Westen GJ, Ijzerman AP, Stieger B, de Witte P, Augustijns PF, Annaert PP.
Abstract : Several recent studies show that inhibition of the hepatic transport proteins organic anion-transporting polypeptide 1B1 (OATP1B1) and 1B3 (OATP1B3) can result in clinically relevant drug-drug interactions (DDI). To avoid late-stage development drug failures due to OATP1B-mediated DDI, predictive in vitro and in silico methods should be implemented at an early stage of the drug candidate evaluation process. In the present study, we first developed a high-throughput in vitro transporter inhibition assay for the OATP1B subfamily. A total of 2000 compounds were tested as potential modulators of the uptake of the OATP1B substrate sodium fluorescein, in OATP1B1- or 1B3-transfected Chinese hamster ovary cells. At an equimolar substrate-inhibitor concentration of 10 µM, 212 and 139 molecules were identified as OATP1B1 and OATP1B3 inhibitors, respectively (minimum 50% inhibition). For 69 compounds, previously not identified as OATP1B inhibitors, concentration-dependent inhibition was also determined, yielding Ki values ranging from 0.06 to 6.5 µM. Based on these in vitro data, we subsequently developed a proteochemometrics-based in silico model, which predicted OATP1B inhibitors in the test group (20% of the dataset) with high specificity (86%) and sensitivity (78%). Moreover, several physicochemical compound properties and substructures related to OATP1B1/1B3 inhibition or inactivity were identified. Finally, model performance was prospectively verified with a set of 54 compounds not included in the original dataset. This validation indicated that 80 and 74% of the compounds were correctly classified for OATP1B1 and OATP1B3 inhibition, respectively.
|
Inhibition of sodium fluorescein uptake in OATP1B3-transfected CHO cells at an equimolar substrate-inhibitor concentration of 10 uM
|
Cricetulus griseus
|
105.34
%
|
|
Journal : Mol. Pharmacol.
Title : Structure-based identification of OATP1B1/3 inhibitors.
Year : 2013
Volume : 83
Issue : 6
First Page : 1257
Last Page : 1267
Authors : De Bruyn T, van Westen GJ, Ijzerman AP, Stieger B, de Witte P, Augustijns PF, Annaert PP.
Abstract : Several recent studies show that inhibition of the hepatic transport proteins organic anion-transporting polypeptide 1B1 (OATP1B1) and 1B3 (OATP1B3) can result in clinically relevant drug-drug interactions (DDI). To avoid late-stage development drug failures due to OATP1B-mediated DDI, predictive in vitro and in silico methods should be implemented at an early stage of the drug candidate evaluation process. In the present study, we first developed a high-throughput in vitro transporter inhibition assay for the OATP1B subfamily. A total of 2000 compounds were tested as potential modulators of the uptake of the OATP1B substrate sodium fluorescein, in OATP1B1- or 1B3-transfected Chinese hamster ovary cells. At an equimolar substrate-inhibitor concentration of 10 µM, 212 and 139 molecules were identified as OATP1B1 and OATP1B3 inhibitors, respectively (minimum 50% inhibition). For 69 compounds, previously not identified as OATP1B inhibitors, concentration-dependent inhibition was also determined, yielding Ki values ranging from 0.06 to 6.5 µM. Based on these in vitro data, we subsequently developed a proteochemometrics-based in silico model, which predicted OATP1B inhibitors in the test group (20% of the dataset) with high specificity (86%) and sensitivity (78%). Moreover, several physicochemical compound properties and substructures related to OATP1B1/1B3 inhibition or inactivity were identified. Finally, model performance was prospectively verified with a set of 54 compounds not included in the original dataset. This validation indicated that 80 and 74% of the compounds were correctly classified for OATP1B1 and OATP1B3 inhibition, respectively.
|
Antitumor activity against mouse EAC allografted in CF1 mouse assessed as tumor growth inhibition at 20 mg/kg, ip qd for 7 days (Rvb = 0%)
|
Mus musculus
|
99.6
%
|
|
Journal : J. Med. Chem.
Title : Antitumor and antiinflammatory agents: N-benzoyl-protected cyanomethyl esters of amino acids.
Year : 1979
Volume : 22
Issue : 11
First Page : 1419
Last Page : 1422
Authors : Sajadi Z, Almahmood M, Loeffler LJ, Hall IH.
Abstract : A series of N-protected cyanomethyl esters of various amino acids was synthesized and tested for antineoplastic and antiinflammatory activity in rodents. Utilizing the L-phenylalanine cyanomethyl ester and varying the N-protecting moiety demonstrated that the N-tosyl and the N-Cbz analogues were the most active against Ehrlich ascites cell proliferation. The N-(carbobenzyloxy)- and N-benzoyl-L-phenylalanine cyanomethyl esters were the most active against carrageenan-induced inflammation. In the N-benzoyl series of cyanomethyl esters, L-alanine, DL-valine, and L-leucine amino acid analogues were the most active against Ehrlich ascites cell proliferation. The glycine and L-alanine analogues possessed the best inhibitor activity in the antiinflammatory screen. The cyanomethyl esters also demonstrated immunosuppressive activity and the ability to suppress the writhing reflex which is associated with inflammatory pain. However, no antipyretic or narcotic analgesic activity was demonstrated by these agents.
|
Antitumor activity against mouse EAC allografted in CF1 mouse assessed as inhibition of tumor growth at 33 mg/kg/day measured on day 7
|
Mus musculus
|
99.6
%
|
|
Journal : J. Med. Chem.
Title : Antineoplastic agents. 1. N-Protected vinyl, 1,2-dihaloethyl, and cyanomethyl esters of phenylalanine.
Year : 1977
Volume : 20
Issue : 12
First Page : 1578
Last Page : 1584
Authors : Loeffler LJ, Sajadi Z, Hall IH.
Abstract : A series of N-protected vinyl, 1,2-dihaloethyl, and cyanomethyl esters of phenylalanine was synthesized and these compounds were evaluated for antitumor activity against the growth of Ehrlich ascites carcinoma in CF1 male mice (33 mg/kg/day), Walker 256 carcinosarcoma in Sprague-Dawley male rats (2.5 mg/kg/day), and P388 lymphocytic leukemia in DBA/2 mice (20 mg/kg/day). Structure-activity relationships were evaluated and acute toxicity studies (LD50 determinations) in male CF1 mice were also carried out on selected compounds. Carbobenzoxy-L0phenylalanine vinyl ester (5), N-carbobenzoxy-L-phenylalanine 1,2-dibromoethyl ester (12), and N-carbobenzoxy-L-phenylalanine cyanomethyl ester (8) were found to be very potent inhibitors of Ehrlich ascites tumor growth at nontoxic doses cited above. Compounds 5 and 12 also tripled survival time in the Walker 256 system. LD50 values for compounds 5, 12, and 8 were greater than 2000 mg/kg (greater than 6.15 mmol/kg), 74 mg/kg (0.15 mmol/kg), and 150 mg/kg (0.44 mmol/kg), respectively.
|
Inhibition of IDO1 (unknown origin) at highest soluble concentration using L-tryptophan substrate incubated for 60 mins by HPLC
|
Homo sapiens
|
0.5
%
|
|
Journal : Eur. J. Med. Chem.
Title : Detailed analysis and follow-up studies of a high-throughput screening for indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors.
Year : 2014
Volume : 84
First Page : 284
Last Page : 301
Authors : Röhrig UF, Majjigapu SR, Chambon M, Bron S, Pilotte L, Colau D, Van den Eynde BJ, Turcatti G, Vogel P, Zoete V, Michielin O.
Abstract : Indoleamine 2,3-dioxygenase 1 (IDO1) is a key regulator of immune responses and therefore an important therapeutic target for the treatment of diseases that involve pathological immune escape, such as cancer. Here, we describe a robust and sensitive high-throughput screen (HTS) for IDO1 inhibitors using the Prestwick Chemical Library of 1200 FDA-approved drugs and the Maybridge HitFinder Collection of 14,000 small molecules. Of the 60 hits selected for follow-up studies, 14 displayed IC50 values below 20 μM under the secondary assay conditions, and 4 showed an activity in cellular tests. In view of the high attrition rate we used both experimental and computational techniques to identify and to characterize compounds inhibiting IDO1 through unspecific inhibition mechanisms such as chemical reactivity, redox cycling, or aggregation. One specific IDO1 inhibitor scaffold, the imidazole antifungal agents, was chosen for rational structure-based lead optimization, which led to more soluble and smaller compounds with micromolar activity.
|
PubChem BioAssay. RKO viability from Cell TiterGlo-IC50. (Class of assay: confirmatory)
|
None
|
659.1
nM
|
|
Title : PubChem BioAssay data set
|
PubChem BioAssay. HCT116 viability from Cell TiterGlo-IC50. (Class of assay: confirmatory)
|
None
|
259.1
nM
|
|
Title : PubChem BioAssay data set
|
PubChem BioAssay. VEGF stimulated ADSC/ECFC co-culture CD31-stained tube area decrease-IC50. (Class of assay: confirmatory)
|
None
|
914.9
nM
|
|
Title : PubChem BioAssay data set
|
PubChem BioAssay. HT-29 viability from Cell TiterGlo-IC50. (Class of assay: confirmatory)
|
None
|
634.55
nM
|
|
Title : PubChem BioAssay data set
|
PubChem BioAssay. DLD-1 viability from Cell TiterGlo-IC50. (Class of assay: confirmatory)
|
None
|
259.81
nM
|
|
Title : PubChem BioAssay data set
|
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
|
22.75
%
|
|
|
Antibacterial activity against Escherichia coli ATCC 25922 (CO-ADD:GN_001); MIC in CAMBH media using NBS plates, by OD(600)
|
Escherichia coli
|
6.85
%
|
|
|
Antibacterial activity against Klebsiella pneumoniae MDR ATCC 70063 (CO-ADD:GN_003); MIC in CAMBH media using NBS plates, by OD(600)
|
Klebsiella pneumoniae
|
7.84
%
|
|
|
Antibacterial activity against Pseudomonas aeruginosa ATCC 27853 (CO-ADD:GN_042); MIC in CAMBH media using NBS plates, by OD(600)
|
Pseudomonas aeruginosa
|
11.75
%
|
|
|
Antibacterial activity against Acinetobacter baumannii ATCC 19606 (CO-ADD:GN_034); MIC in CAMBH media using NBS plates, by OD600
|
Acinetobacter baumannii
|
19.41
%
|
|
|
Antifungal activity against Candida albicans ATCC 90028 (CO-ADD:FG_001); MIC in YNB media using NBS plates, by OD630
|
Candida albicans
|
11.25
%
|
|
|
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
|
-0.87
%
|
|
|
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
|
3.56
%
|
|
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.
|
Inhibition of UDPGDH in rat hepatocytes assessed as decrease in bilirubin monoglucuronide level at 50 uM preincubated for 2 mins followed by UDPGA addition measured after 45 mins by HPLC analysis relative to control
|
Rattus norvegicus
|
28.0
%
|
|
Journal : MedChemComm
Title : Efforts in redesigning the antileukemic drug 6-thiopurine: decreasing toxic side effects while maintaining efficacy.
Year : 2019
Volume : 10
Issue : 1
First Page : 169
Last Page : 179
Authors : Torres Hernandez AX, Weeramange CJ, Desman P, Fatino A, Haney O, Rafferty RJ.
Abstract : 6-Thiopurine (6TP) is a currently prescribed drug in the treatment of diseases ranging from Crohn's disease to acute lymphocytic leukemia. While its potent mode of action is through incorporation into DNA as a thiol mimic of deoxyguanosine, severe toxicities are associated with its administration which hinder the potential therapeutic application. We have previously reported <i>in vitro</i> that the oxidative metabolites of 6TP, specifically 6-thiouric acid (6TU, <i>K</i> <sub>i</sub> 7 μM), are potent inhibitors of UDP-glucose dehydrogenase (UDPGDH), an enzyme that is responsible for the formation of UDP-glucuronic acid (UDPGA), an essential substrate that is used in detoxification processes in the liver. An <i>in vivo</i> investigation was undertaken to probe if 6TU inhibits UDPGDH in rat hepatocytes, and it was observed that 6TU does greatly suppress the conjugation of bilirubin with UDPGA. The failed excretion of bilirubin is linked to a majority of the reported toxicities associated with 6TP administration. Efforts were undertaken for the construction of 6TP analogs, substituted at the C8 position, to reduce inhibition of UDPGDH while retaining therapeutic efficacy. Three new 6TP analogs bearing a halogen (Br, Cl, and F) at the C8 position have been achieved over five-synthetic steps in overall yields of 16 to 32%. Each of these analogs were shown to have reduced inhibition towards UDPGDH, with <i>K</i> <sub>i</sub> values of 192, 163, 215 μM, respectively. In addition, the bromine, chlorine, and fluorine analogs were shown to possess cytotoxicity towards the REH cell line (acute lymphocytic leukemia) having IC<sub>50</sub> values of 9.54 μM (±0.97), 3.95 μM (±1.94), and 4.71 μM (±1.40), respectively. These three new 6TP analogs represent the first steps in the redesign of this potent anticancer agent into a better drug that possesses reduced toxic side effects while retaining therapeutic potency.
|
Inhibition of UDPGDH in rat hepatocytes assessed as decrease in bilirubin diglucuronide level at 50 uM preincubated for 2 mins followed by UDPGA addition measured after 45 mins by HPLC analysis relative to control
|
Rattus norvegicus
|
26.0
%
|
|
Journal : MedChemComm
Title : Efforts in redesigning the antileukemic drug 6-thiopurine: decreasing toxic side effects while maintaining efficacy.
Year : 2019
Volume : 10
Issue : 1
First Page : 169
Last Page : 179
Authors : Torres Hernandez AX, Weeramange CJ, Desman P, Fatino A, Haney O, Rafferty RJ.
Abstract : 6-Thiopurine (6TP) is a currently prescribed drug in the treatment of diseases ranging from Crohn's disease to acute lymphocytic leukemia. While its potent mode of action is through incorporation into DNA as a thiol mimic of deoxyguanosine, severe toxicities are associated with its administration which hinder the potential therapeutic application. We have previously reported <i>in vitro</i> that the oxidative metabolites of 6TP, specifically 6-thiouric acid (6TU, <i>K</i> <sub>i</sub> 7 μM), are potent inhibitors of UDP-glucose dehydrogenase (UDPGDH), an enzyme that is responsible for the formation of UDP-glucuronic acid (UDPGA), an essential substrate that is used in detoxification processes in the liver. An <i>in vivo</i> investigation was undertaken to probe if 6TU inhibits UDPGDH in rat hepatocytes, and it was observed that 6TU does greatly suppress the conjugation of bilirubin with UDPGA. The failed excretion of bilirubin is linked to a majority of the reported toxicities associated with 6TP administration. Efforts were undertaken for the construction of 6TP analogs, substituted at the C8 position, to reduce inhibition of UDPGDH while retaining therapeutic efficacy. Three new 6TP analogs bearing a halogen (Br, Cl, and F) at the C8 position have been achieved over five-synthetic steps in overall yields of 16 to 32%. Each of these analogs were shown to have reduced inhibition towards UDPGDH, with <i>K</i> <sub>i</sub> values of 192, 163, 215 μM, respectively. In addition, the bromine, chlorine, and fluorine analogs were shown to possess cytotoxicity towards the REH cell line (acute lymphocytic leukemia) having IC<sub>50</sub> values of 9.54 μM (±0.97), 3.95 μM (±1.94), and 4.71 μM (±1.40), respectively. These three new 6TP analogs represent the first steps in the redesign of this potent anticancer agent into a better drug that possesses reduced toxic side effects while retaining therapeutic potency.
|
Inhibition of UDPGDH in rat hepatocytes assessed as increase in unconjugated bilirubin level at 25 uM preincubated for 2 mins followed by UDPGA addition measured after 45 mins by HPLC analysis relative to control
|
Rattus norvegicus
|
19.0
%
|
|
Journal : MedChemComm
Title : Efforts in redesigning the antileukemic drug 6-thiopurine: decreasing toxic side effects while maintaining efficacy.
Year : 2019
Volume : 10
Issue : 1
First Page : 169
Last Page : 179
Authors : Torres Hernandez AX, Weeramange CJ, Desman P, Fatino A, Haney O, Rafferty RJ.
Abstract : 6-Thiopurine (6TP) is a currently prescribed drug in the treatment of diseases ranging from Crohn's disease to acute lymphocytic leukemia. While its potent mode of action is through incorporation into DNA as a thiol mimic of deoxyguanosine, severe toxicities are associated with its administration which hinder the potential therapeutic application. We have previously reported <i>in vitro</i> that the oxidative metabolites of 6TP, specifically 6-thiouric acid (6TU, <i>K</i> <sub>i</sub> 7 μM), are potent inhibitors of UDP-glucose dehydrogenase (UDPGDH), an enzyme that is responsible for the formation of UDP-glucuronic acid (UDPGA), an essential substrate that is used in detoxification processes in the liver. An <i>in vivo</i> investigation was undertaken to probe if 6TU inhibits UDPGDH in rat hepatocytes, and it was observed that 6TU does greatly suppress the conjugation of bilirubin with UDPGA. The failed excretion of bilirubin is linked to a majority of the reported toxicities associated with 6TP administration. Efforts were undertaken for the construction of 6TP analogs, substituted at the C8 position, to reduce inhibition of UDPGDH while retaining therapeutic efficacy. Three new 6TP analogs bearing a halogen (Br, Cl, and F) at the C8 position have been achieved over five-synthetic steps in overall yields of 16 to 32%. Each of these analogs were shown to have reduced inhibition towards UDPGDH, with <i>K</i> <sub>i</sub> values of 192, 163, 215 μM, respectively. In addition, the bromine, chlorine, and fluorine analogs were shown to possess cytotoxicity towards the REH cell line (acute lymphocytic leukemia) having IC<sub>50</sub> values of 9.54 μM (±0.97), 3.95 μM (±1.94), and 4.71 μM (±1.40), respectively. These three new 6TP analogs represent the first steps in the redesign of this potent anticancer agent into a better drug that possesses reduced toxic side effects while retaining therapeutic potency.
|
Inhibition of UDPGDH in rat hepatocytes assessed as decrease in bilirubin monoglucuronide level at 25 uM preincubated for 2 mins followed by UDPGA addition measured after 45 mins by HPLC analysis relative to control
|
Rattus norvegicus
|
19.0
%
|
|
Journal : MedChemComm
Title : Efforts in redesigning the antileukemic drug 6-thiopurine: decreasing toxic side effects while maintaining efficacy.
Year : 2019
Volume : 10
Issue : 1
First Page : 169
Last Page : 179
Authors : Torres Hernandez AX, Weeramange CJ, Desman P, Fatino A, Haney O, Rafferty RJ.
Abstract : 6-Thiopurine (6TP) is a currently prescribed drug in the treatment of diseases ranging from Crohn's disease to acute lymphocytic leukemia. While its potent mode of action is through incorporation into DNA as a thiol mimic of deoxyguanosine, severe toxicities are associated with its administration which hinder the potential therapeutic application. We have previously reported <i>in vitro</i> that the oxidative metabolites of 6TP, specifically 6-thiouric acid (6TU, <i>K</i> <sub>i</sub> 7 μM), are potent inhibitors of UDP-glucose dehydrogenase (UDPGDH), an enzyme that is responsible for the formation of UDP-glucuronic acid (UDPGA), an essential substrate that is used in detoxification processes in the liver. An <i>in vivo</i> investigation was undertaken to probe if 6TU inhibits UDPGDH in rat hepatocytes, and it was observed that 6TU does greatly suppress the conjugation of bilirubin with UDPGA. The failed excretion of bilirubin is linked to a majority of the reported toxicities associated with 6TP administration. Efforts were undertaken for the construction of 6TP analogs, substituted at the C8 position, to reduce inhibition of UDPGDH while retaining therapeutic efficacy. Three new 6TP analogs bearing a halogen (Br, Cl, and F) at the C8 position have been achieved over five-synthetic steps in overall yields of 16 to 32%. Each of these analogs were shown to have reduced inhibition towards UDPGDH, with <i>K</i> <sub>i</sub> values of 192, 163, 215 μM, respectively. In addition, the bromine, chlorine, and fluorine analogs were shown to possess cytotoxicity towards the REH cell line (acute lymphocytic leukemia) having IC<sub>50</sub> values of 9.54 μM (±0.97), 3.95 μM (±1.94), and 4.71 μM (±1.40), respectively. These three new 6TP analogs represent the first steps in the redesign of this potent anticancer agent into a better drug that possesses reduced toxic side effects while retaining therapeutic potency.
|
Inhibition of UDPGDH in rat hepatocytes assessed as decrease in bilirubin diglucuronide level at 25 uM preincubated for 2 mins followed by UDPGA addition measured after 45 mins by HPLC analysis relative to control
|
Rattus norvegicus
|
12.0
%
|
|
Journal : MedChemComm
Title : Efforts in redesigning the antileukemic drug 6-thiopurine: decreasing toxic side effects while maintaining efficacy.
Year : 2019
Volume : 10
Issue : 1
First Page : 169
Last Page : 179
Authors : Torres Hernandez AX, Weeramange CJ, Desman P, Fatino A, Haney O, Rafferty RJ.
Abstract : 6-Thiopurine (6TP) is a currently prescribed drug in the treatment of diseases ranging from Crohn's disease to acute lymphocytic leukemia. While its potent mode of action is through incorporation into DNA as a thiol mimic of deoxyguanosine, severe toxicities are associated with its administration which hinder the potential therapeutic application. We have previously reported <i>in vitro</i> that the oxidative metabolites of 6TP, specifically 6-thiouric acid (6TU, <i>K</i> <sub>i</sub> 7 μM), are potent inhibitors of UDP-glucose dehydrogenase (UDPGDH), an enzyme that is responsible for the formation of UDP-glucuronic acid (UDPGA), an essential substrate that is used in detoxification processes in the liver. An <i>in vivo</i> investigation was undertaken to probe if 6TU inhibits UDPGDH in rat hepatocytes, and it was observed that 6TU does greatly suppress the conjugation of bilirubin with UDPGA. The failed excretion of bilirubin is linked to a majority of the reported toxicities associated with 6TP administration. Efforts were undertaken for the construction of 6TP analogs, substituted at the C8 position, to reduce inhibition of UDPGDH while retaining therapeutic efficacy. Three new 6TP analogs bearing a halogen (Br, Cl, and F) at the C8 position have been achieved over five-synthetic steps in overall yields of 16 to 32%. Each of these analogs were shown to have reduced inhibition towards UDPGDH, with <i>K</i> <sub>i</sub> values of 192, 163, 215 μM, respectively. In addition, the bromine, chlorine, and fluorine analogs were shown to possess cytotoxicity towards the REH cell line (acute lymphocytic leukemia) having IC<sub>50</sub> values of 9.54 μM (±0.97), 3.95 μM (±1.94), and 4.71 μM (±1.40), respectively. These three new 6TP analogs represent the first steps in the redesign of this potent anticancer agent into a better drug that possesses reduced toxic side effects while retaining therapeutic potency.
|
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate
|
Severe acute respiratory syndrome coronavirus 2
|
-11.49
%
|
|
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
|
0.14
%
|
|
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
|
0.14
%
|
|
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.
