New (3-(1<i>H</i>-benzo[<i>d</i>]imidazol-2-yl))/(3-(3<i>H</i>-imidazo[4,5-<i>b</i>]pyridin-2-yl))-(1<i>H</i>-indol-5-yl)(3,4,5-trimethoxyphenyl)methanone conjugates as tubulin polymerization inhibitors.
Mullagiri K, Nayak VL, Sunkari S, Mani GS, Guggilapu SD, Nagaraju B, Alarifi A, Kamal A.
A series of new (3-(1<i>H</i>-benzo[<i>d</i>]imidazol-2-yl))/(3-(3<i>H</i>-imidazo[4,5-<i>b</i>]pyridin-2-yl))-(1<i>H</i>-indol-5-yl)(3,4,5-trimethoxyphenyl)methanone conjugates <b>4-6(a-i)</b> 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<sub>50</sub> values ranging from 0.54 to 31.86 μM. Among them, compounds <b>5g</b> and <b>6f</b> showed significant activity against human prostate cancer cell line DU-145 with IC<sub>50</sub> 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 (<b>5g</b> and <b>6f</b>) was confirmed by Hoechst staining, measurement of mitochondrial membrane potential and ROS generation and annexin V-FITC assays.