Synthesis, In Silico Evaluation, and Biological Activity Assessment of Chalcone Derivatives Against MCF-7 Cells

Chalcones, characterized by their distinct α,β-unsaturated carbonyl system, exhibit diverse therapeutic properties, including antimicrobial and anticancer activities. The current study focused on synthesizing novel chalcone derivatives using a base-catalyzed Claisen–Schmidt condensation reaction involving substituted benzaldehydes and acetophenone derivatives. These synthesized compounds were structurally verified using FTIR, ¹H NMR, and ¹³C NMR spectroscopy, confirming the successful formation of chalcones via characteristic carbonyl and olefinic peaks. Biological evaluation included cytotoxic assays against the MCF-7 breast cancer cell line, using the MTT assay, where derivative 1C displayed significant cytotoxicity (approximately 10.93% cell viability at 320 ppm), markedly surpassing derivative 1A. Furthermore, antibacterial activities assessed through the agar diffusion method demonstrated pronounced inhibitory effects against Bacillus subtilis, Escherichia coli, and Streptococcus pneumoniae, with compound 1A exhibiting superior antibacterial activity. Additionally, molecular docking studies revealed that derivative 1C showed promising binding affinity (-7.69 kcal/mol) and favorable interactions with key amino acid residues within the estrogen receptor (PDB ID: 5T92), highlighting its potential mechanism of action. These findings emphasize the critical influence of structural variations on biological outcomes and suggest that further optimization of chalcone derivatives with different substitution patterns could yield potent, multifunctional therapeutic agents.