PREDICTION OF ANTI-LUNG CANCER POTENTIAL OF TRADITIONAL MEDICINAL PLANT-DERIVED COMPOUNDS: A COMPREHENSIVE IN SILICO ANALYSIS

Abstract

Lung cancer remains the leading cause of cancer-related deaths worldwide, claiming more lives annually than prostate, breast, and colon cancers combined. Limited resources for prognosis and the rising costs of screening and treatment contribute to this challenge, emphasizing the need for efficient therapeutics. Thus, following a repurposing approach, we investigated the interaction of 108 plant-derived compounds (PDCs) with the lung cancer-associated protein Keap1 (PDB ID: 1X2J). Various analyses—including pkCSM for pharmacokinetic properties, swissADME for ADME profiling, CLC-Pred 2.0 for cytotoxicity assessments, and molecular docking—led to the identification of 15 PDCs as promising candidates for lung cancer therapy. Further, the research highlighted six key ligands—Sesamin, Asiatic acid, Tubulosine, Chrysophanic acid, Bavachinin, and Chrysin—as particularly effective therapeutic agents. These compounds exhibit superior binding affinities compared to the synthetic drugs MSU38225 Gemcitabine and VBQ, with values ranging from -10.4 kcal/mol to -9.3 kcal/mol for the target protein. They also demonstrate notable cytotoxic effects against lung cancer cell lines A549 and A549/TR, strengthening their potential as viable treatment options.