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 IC50 = 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 Scheme 1, Scheme 2 and Scheme 3. Their antitumor activity was evaluated against MCF-7 cell line. Compound 3e was more potent than vincristine. Docking study suggested their antitubulin activity. Figure optionsDownload as PowerPoint slideHighlights
► Different 2-phenylindole derivatives were prepared.
► They were tested against MCF-7 cell line.
► One compound 3e (IC50 = 1.60 nM) was more potent than vincristine (IC50 = 2.00 nM).
► The active compounds were successfully docked into tubulin.