In silico analysis, isolation, and cytotoxicity evaluation of the coumestans from Cullen corylifolium (L.) Medik

Cullen corylifolium is well known for diverse phytoconstituents that possess multifaceted pharmacology, and one such less explored class is coumestans, which have not been well explored for their anticancer activities. One of the popular cancer targets is the Epidermal Growth Factor Receptor, a tyrosine kinase involved in various cancers, especially breast and lung cancer hence, a crucial cancer target. This work is focussed on molecular docking and molecular simulation studies on coumestans against EGFR. The rigorous docking studies resulted in two coumestans (1 and 5) with binding energy less than Gefitinib and Erlotinib. Compounds 1 and 5 were subjected to molecular simulation, binding free energy calculation, per-residue energy decomposition, and in silico ADMET prediction. The best hit, compound 1 was evaluated for its cytotoxicity against MDA-MB-231 and A549 cells via in vitro assay. The ligand-protein complex exhibited good stability, binding free energies, better in silico pharmacokinetics, low toxicity, and good cytotoxicity.