Discovery of 1H-benzo[d][1,2,3]triazol-1-yl 3,4,5-trimethoxybenzoate as a potential antiproliferative agent by inhibiting histone deacetylase.
Twenty-one benzotriazoles (3-16 and 18-24) were synthesized and half of them (5, 8-16, 20, and 21) were reported for the first time. Their antiproliferative activities against three human cancer cells were assayed. It revealed that 1H-benzo[d][1,2,3]triazol-1-yl 3,4,5-trimethoxybenzoate (9) showed considerable activity against three human cancer cell lines with the half maximal inhibitory concentration (IC(50)) values of 1.2-2.4 nM, which were close to the value of the positive control, doxorubicin. Further investigation indicated compound 9 was a potential histone deacetylase inhibitor (IC(50)=9.4 μM) and its binding mode was simulated using docking method.
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, People's Republic of China.
Jie
J
Fu
Ying
Y
Yang
Xue-Wei
XW
Zhang
Wen-Jun
WJ
Mao
Zhi-Ming
ZM
Zhang
Hai-Liang
HL
Zhu
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001565:Benzoates / Q000138:chemical synthesis* / Q000494:pharmacology; D001665:Binding Sites; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology; D055808:Drug Discovery; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D011485:Protein Binding; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis / Q000494:pharmacology
D000970:Antineoplastic Agents; D001565:Benzoates; D056572:Histone Deacetylase Inhibitors; D014230:Triazoles; D004317:Doxorubicin