Integrated molecular docking, simulation dynamics and cytotoxicity assays of Desmodium gangeticum-derived phytochemicals for multi-target cancer therapy.

UNLABELLED: Cancer continues to be a significant worldwide health concern, requiring ongoing research into new and efficient treatment options. This study used an integrated in-vitro and in-silico strategy to systematically examine the anticancer potential of phytoconstituents produced by Desmodium gangeticum (Linn.). Using phytochemicals found in the root and shoot extracts, molecular docking investigations were carried out against three important cancer-associated targets: BCL-XL, translocator protein (TSPO), and tubulin. With docking scores of - 7.27 and - 8.15, respectively, squalene and benzenamine, 4,4'-ethylidenebis [N, N-diethyl-3-methyl-], showed significant binding affinities toward BCL-XL, TSPO, and tubulin among the root-derived compounds. From among the shoot-derived compounds, stigmasterol had the highest affinity for TSPO (- 11.81 kcal/mol) and tubulin (- 8.17 kcal/mol), while γ-sitosterol showed the strongest binding association with BCL-XL (- 9.39 kcal/mol). BIOVIA Discovery Studio was used to visualise protein-ligand interactions, and SwissADME was used to assess the lead compounds' drug-likeness and pharmacokinetic profiles in compliance with Lipinski and Veber's guidelines. The stability and conformational flexibility of the γ-sitosterol protein complexes throughout a 50-ns trajectory were further validated by molecular dynamics simulations. The chloroform root extract showed the highest antiproliferative activity against OVCAR-3 and HeLa cancer cell lines. Collectively, these findings highlight D. gangeticum as a promising source of bioactive compounds with significant anticancer potential, warranting further mechanistic and preclinical investigations. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at https://doi.org/10.1007/s40203-026-00748-8.