Synthesis and Characterization of Acridin‐9(10h)‐One (A9O) Derivatives: In Silico Structure–Property Insights into EGFR Targeting and Antioxidant Potential

Abstract

This study reports the synthesis, characterization, and computational investigation of five acridin‐9(10H)‐one (A9O) derivatives ( 4a–4e ) using DFT methods. Compound 4c , bearing chloro and trifluoromethyl substituents, exhibited distinctive electronic properties and was further characterized by FT‐IR, 1 H, 1 3 C, and 1 9 F NMR spectroscopy and mass spectrometry. Frontier molecular orbital, Fukui, QTAIM, ELF, IRI, and LOL analyses provided insights into electronic structure, reactivity, and bonding characteristics. TD‐DFT calculations using CAM‐B3LYP predicted an absorption maximum of 450.685 nm for 4c . Molecular docking and dynamics studies with EGFR indicated favorable ligand interactions and complex stability. Experimentally, 4c showed significant DPPH radical‐scavenging activity (76.24%). ADMET predictions further indicated favorable pharmacokinetic characteristics, supporting its potential for biological applications.