Abstract

STRUCTURE-BASED DISCOVERY OF ISOFLAVONE DERIVATIVES TARGETING EGFR IN NSCLC: AN INTEGRATED IN SILICO STUDY USING DOCKING, ADMET, AND DFT APPROACHES

Abul Bashar Ripon Khalipha* and Md. Mehedi Hasan

ABSTRACT

Non-Small Cell Lung Cancer (NSCLC) remains a significant global health challenge, with the Epidermal Growth Factor Receptor (EGFR) being a key therapeutic target. This study employed a comprehensive in silico approach to design and evaluate a series of novel isoflavone derivatives as potential EGFR inhibitors. Molecular docking studies were performed to assess the binding affinities and interaction patterns of these derivatives within the ATP-binding site of EGFR. Subsequently, Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) properties, along with drug-likeness parameters, were predicted using established computational tools. Promising candidates identified through docking and ADMET screening were further subjected to Density Functional Theory (DFT) calculations to investigate their electronic structures and reactivity descriptors. Several isoflavone derivatives exhibited strong predicted binding affinities to EGFR, forming key interactions with active site residues. These compounds also demonstrated favorable ADMET profiles, adhering to drug-likeness criteria. DFT analysis provided insights into their stability and electronic characteristics. The findings suggest that specific novel isoflavone derivatives hold promise as lead compounds for the development of new EGFR inhibitors for NSCLC therapy, warranting further experimental validation.

Keywords: In Silico Drug Design, EGFR, Non-Small Cell Lung Cancer, Isoflavones, Molecular Docking, ADMET, DFT, CADD.