Anticancer activity of 4-aryl-1,4-dihydropyridines

We have synthesized 22 symmetric and asymmetric 4-aryl-1,4-dihydropyridines (1,4-DHPs) by a “green” microwave-assisted one-pot multicomponent Hantzsch reaction and evaluated their cy-totoxicity to three human cancer cell lines viz. U-251MG (human glioblastoma), HeLa 229 (human cervical adenocarcinoma), and MCF-7 (human breast carcinoma). None of the 1,4-DHPs were cytotoxic to U-251MG cells. Most of the 1,4-DHPs did not affect HeLa 229 or MCF-7 cell viability. On the other hand, the symmetric 1,4-DHPs 18 ((±)-diethyl 4-(4-benzyloxyphenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate), 19 ((±)-diethyl 4-(4-bromophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate), and 20 ((±)-diethyl 4-(3-fluor-4-hydroxyphenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate) reduced HeLa (IC50 = 3.6, 2.3, and 4.1 µM, respectively) and MCF-7 (IC50 = 5.2, 5.7, and 11.9 µM, respectively) cell viability. These 1,4-DHPs were more cytotoxic to HeLa and MCF-7 cells than to GM07492 (normal human fibroblast) cells, as evidenced by their selectivity indexes. Therefore,1,4-DHPs 18, 19, and 20 may serve as novel lead compounds to discover other 1,4-DHP derivatives with improved anti-cancer potency and selectivity.