Design, synthesis, and in-silico study of new letrozole derivatives as prospective anticancer and antioxidant agents

Abstract A new series of derivatives (compounds 8–20) of the breast antihormonal drug letrozole tagged with additional aryl groups were synthesized starting from the letrozole analog 7 via Suzuki cross-coupling reaction. Treatment of the ketone 9 with various aldehydes in base afforded the chalcone analogs 21–27. The structural assignments were done by IR, 1H, 13C and 2D NMR spectra. Compounds 13, 21–23, 25 and 26 have been selected for their anticancer activity against MCF-7 and WRL-68 cell lines. Compounds 13 and 22 were found to be the most potent anticancer agents with IC50 values of 34.75 and 58.79 (μg mL−1) (SI = 3.3 and 2.6, respectively). Molecular docking study of compounds 13 and 22 revealed hydrogen bond with the amino acids Arg115, Met374 and Met364 residues of the receptor 3EQM, respectively. Therefore, compounds 13 and 22 can be considered as promising anticancer agents due to their potent cytotoxic activity.