Synthesis of Novel Indole Derivatives, Antiproliferative Activity, Apoptosis, and Molecular Docking Studies

Abstract

Novel indole-containing analogs were synthesized via a one-pot, multi-component Passerini reaction and subsequently evaluated for their anticancer activity against HeLa, MCF-7, and A549 cancer cell lines using the MTT assay. Among the synthesized compounds, (2-(cyclohexylamino)-1-(3-fluorophenyl)-2-oxoethyl 2-(1H-indol-3-yl)acetate (4f), which demonstrated the most potent cytotoxic activity, exhibited promising results with IC₅₀ values of 17.71 and 19.92 μM against HeLa and MCF-7 cells, respectively. Flow cytometry analysis confirmed that compound 4f significantly induced apoptosis in HeLa cells in a concentration-dependent manner. Furthermore, molecular docking studies into the active site of the anti-apoptotic protein Bcl-xL indicated that compound 4f binds with good affinity, which is consistent with its considerable efficacy in the in vitro tests.