Synthesis and Anticancer Evaluation of -Alkylated (-Chalcone Derivatives: A Focus on Estrogen Receptor Inhibition.

Cancer remains a leading cause of morbidity and mortality worldwide, highlighting the urgent need for novel therapeutic agents. This study investigated the synthesis and biological evaluation of -alkyl ()-chalcone derivatives (-) as potential anticancer agents. The compounds were synthesized via aldol condensation of substituted aldehydes and acetophenones, with structures confirmed by IR, NMR, and mass spectrometry. In vitro cytotoxicity assays revealed varying effectiveness, with compounds , , , and exhibiting potent activity against MDA-MB-231 and MCF-7, showing IC values between 2.08 and 13.58 µM, besides HCT-116 and HeLa cancer cell lines (IC values between 6.59 and 22.64 µM). Notably, compound displayed remarkable selectivity, with an IC of 54.59 µM against the non-cancerous WI-38 cell line. Additionally, protein kinase inhibition assays indicated that compounds and effectively inhibited EGFR and VEGFR-2, with outperforming the standard inhibitor erlotinib. Molecular docking studies of compound showed strong binding affinities in the ATP-binding pockets of EGFR, HER2, VEGFR2, and CDK2. In silico analyses further highlighted the favorable pharmacokinetic properties of compound , underscoring its potential as a selective tyrosine kinase inhibitor. These findings suggest the therapeutic promise of -alkyl ()-chalcone derivatives in cancer treatment.