New (3-(1 H -benzo[ d ]imidazol-2-yl))/(3-(3 H -imidazo[4,5- b ]pyridin-2-yl))-(1 H -indol-5-yl)(3,4,5-trimethoxyphenyl)methanone conjugates as tubulin polymerization inhibitors.

A series of new (3-(1 H -benzo[ d ]imidazol-2-yl))/(3-(3 H -imidazo[4,5- b ]pyridin-2-yl))-(1 H -indol-5-yl)(3,4,5-trimethoxyphenyl)methanone conjugates 4-6(a-i) were synthesized and evaluated for their antiproliferative activity on selected human cancer cell lines such as prostate (DU-145), lung (A549), cervical (HeLa) and breast (MCF-7). Most of these conjugates showed considerable cytotoxicity with IC ₅₀ values ranging from 0.54 to 31.86 μM. Among them, compounds 5g and 6f showed significant activity against human prostate cancer cell line DU-145 with IC ₅₀ values of 0.68 μM and 0.54 μM, respectively. Tubulin polymerization assay and immunofluorescence analysis results suggest that these compounds effectively inhibit microtubule assembly formation in DU-145. Further, the apoptosis-inducing ability of these derivatives ( 5g and 6f ) was confirmed by Hoechst staining, measurement of mitochondrial membrane potential and ROS generation and annexin V-FITC assays.