Structure-activity relationship of indolylkojylmethane based on antiproliferative activity against breast cancer

Abstract

A series of indolylkojylmethane (IKM) derivatives (1–23) was synthesized using a multicomponent one-pot reaction under solvent-free condition using a heterogeneous catalyst. The synthesized compounds were screened against breast cancer cell lines MDA-MB-231, MCF7, and T47D. The structure-activity relationship revealed that IKM synthesized from aliphatic aldehydes (9–11) were active against all three cell lines and showed IC50 value of 0.15 μM–3.93 μM. IKM synthesized from aromatic aldehydes having electron-donating group (1,5, and 6) specifically inhibited the proliferation of the MDA-MB-231 cell line. The effect of various substituted indoles (12–17) was also studied and observed that compound 14 synthesized from 5-cyanoindole, specifically inhibited T47D cell line proliferation. Replacing indole (1) with nucleophiles (18–23) in IKM decreased the antiproliferative activity. Compound 10synthesized from kojic acid, indole and octanal was found to be most potent with IC50 values of 0.21, 0.15, and 3.45 μM against MDA-MB-231, MCF7, and T47D, respectively. © 2020 Wiley-VCH GmbH.