A series of 1H-indol-3-yl-N-phenylacetamide derivatives (F1-14) are synthesized via one-pot Ugi reaction and evaluated for anti-cancer activity against MCF-7, A549, and SKOV3 cell lines. Chloro (F4) and bromo (F5) derivatives exhibit potent cytotoxicity against MCF-7 with higher selectivity than doxorubicin. Flow cytometry and molecular docking confirm Bcl-xL inhibition and apoptosis induction by F5.

Abstract

A series of 1H-indol-3-yl-N-phenylacetamide derivatives (F1-14) were synthesized through a one-pot, multi-component Ugi reaction. The compounds were evaluated as anticancer agents against human breast MCF-7, human lung A549, and human ovarian SKOV3 cancer cell lines. promising results were obtained by C-4 chloro and C-4 bromo-containing derivatives (F4 and F5) against all tested cell lines with good results against MCF-7 cancer cells (IC₅₀ = 12.97 and 10.62 µM, respectively). All compounds exhibited a higher selectivity index (SI) than doxorubicin. Further assessment by flow cytometry analysis showed strong apoptotic cell death induced by the most potent compound F5 in MCF-7 cancer cells. Molecular docking studies strongly confirmed the experimental findings and revealed possible binding modes of these derivatives in the active site of antiapoptotic protein, Bcl-xL (Figure S1).