Harnessing In Silico and In Vitro Approaches to Characterize Alkylated Naringenin Derivatives as Antibreast Cancer Agents

Abstract This study explores the synthesis and characterization of naringenin alkyl derivatives as potential anticancer agents targeting breast cancer‐related hormonal proteins (EGFR, ESR‐α, ESR‐β, HER2, and PR). Docking studies revealed strong binding affinities (−6 to −10 kcal/mol) of synthesized compound, while molecular dynamics simulations confirmed their stable interactions within protein pockets. A novel chalcone derivative, identified via NMR and mass spectrometry, showed enhanced anticancer activity with an IC 50 of 140 µM compared to 166 µM for native naringenin in MTT assays on MCF‐7 cells. The compounds displayed selective toxicity, sparing noncancerous HEK293 cells, even at high concentrations. Drug‐likeness and pharmacokinetic profiles, evaluated using SWISS‐ADME, further support their therapeutic potential. This research underscores the improved methodology for synthesis and utility of computer‐aided drug design (CADD) in developing novel scaffolds to improve the pharmacokinetics and anticancer properties of naringenin derivatives.