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Synthesis of Novel Indolyl‐1,2,4‐triazoles as Potent and Selective Anticancer Agents
Author(s) -
Kumar Dalip,
Narayanam Maruthi Kumar,
Chang KueiHua,
Shah Kavita
Publication year - 2011
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2010.01051.x
Subject(s) - cytotoxicity , stereochemistry , chemistry , indole test , cell culture , 1,2,3 triazole , ic50 , cancer cell lines , combinatorial chemistry , in vitro , cancer cell , biochemistry , biology , cancer , genetics
A diverse series of 22 indolyl‐1,2,4‐triazole congeners (6 and 7) have been synthesized from the reaction of indole‐3‐carbonitrile (4) or (5) with appropriate acid hydrazides in the presence of potassium carbonate. Synthesized compounds were evaluated for their cytotoxicity against six human cancer cell lines, and some of the compounds displayed promising activity. In particular, 3‐(3′,4′,5′‐trimethoxyphenyl)‐5‐( N ‐methyl‐3′‐indolyl)‐1,2,4‐triazole (7i) and 3‐(4′‐piperidinyl)‐5‐( N ‐methyl‐3′‐indolyl)‐1,2,4‐triazole (7n) were the most promising and broadly active compounds against the tested cell lines. It was interesting to note that the trimethoxyphenyl analog 7i showed twofold selective cytotoxicity against PaCa2 cell line (IC 50 0.8 μ m ), whereas piperidinyl analog 7n was found to be selectively cytotoxic against MCF7 cell line (IC 50 1.6 μ m ). Notably, the 4‐fluorophenyl derivative 7c exhibited selective cytotoxicity against PC3 cell line (IC 50 4 μ m ). The structure–activity relationship study revealed that substituents including 3,4,5‐trimethoxyphenyl, 3,4‐dimethoxyphenyl, 4‐benzyloxy‐3‐methoxyphenyl, 4‐piperidinyl, 4‐fluorophenyl and N ‐methylindole are beneficial for the activity of indolyl‐1,2,4‐triazoles (6 and 7).