Synthesis, molecular docking study and antitumor activity of novel 2-phenylindole derivatives

The starting material, 4-(1-indol-2-yl)phenol 1 was obtained via Fischer synthesis. Vilsmeir Haack ’s formylation of 1 gave the carboxaldehyde derivative 2 which was subjected to different reactions affording the 3-substituted compounds 3– 10. Compound 1 reacted with halo esters to give 11 and 12a, b. The reaction of 12a with various amino derivatives gave compounds 13– 16. The hydrazide derivative 15a reacted with 1,3-diketones, ethyl acetoacetate and aromatic carboxylic acid derivatives to give 17a, b, 18 and 19a– e, respectively. Antitumor activity of target compounds were tested against breast cancer cell lines (MCF-7) and (MDA-MB-231). The most potent compound was 3e with IC 50 = 1.60 nM against (MCF-7). Docking was performed on colchicine binding site of tubulin to study the binding mode of the designed compounds. Several 3-(un)substituted-2-phenylindoles were synthesized according to Schemes 1–3. Their antitumor activity was evaluated against MCF-7 cell line. Compound 3e was more potent than vincristine. Docking study suggested their antitubulin activity. [Display omitted] ► Different 2-phenylindole derivatives were prepared. ► They were tested against MCF-7 cell line. ► One compound 3e (IC 50 = 1.60 nM) was more potent than vincristine (IC 50 = 2.00 nM). ► The active compounds were successfully docked into tubulin.