In Vitro Evaluation of Anticancer and Apoptotic Activity of Elaeagnus caudata Schltdl. With Computational Identification of a Novel HSP90 Inhibitor

ABSTRACT Despite its extensive traditional use in treating various illnesses, including cancer, Elaeagnus caudata remains neglected and relatively unexplored in terms of its pharmacological potential. This study addressed the anticancer potential of E. caudata . The methanolic extract of E. caudata leaves was fractioned. The B2 fraction was identified as the most cytotoxic, with the lowest IC 50 against A549 and HCT116 cells. The B2 fraction activities were further supported by a higher apoptotic index, increased caspase‐3/6 activity, DNA damage, and elevated lipid peroxidation with decreasing antioxidant levels. LC–MS analysis revealed 12 major compounds in the B2 fraction, with amorphigenin emerging as a promising drug candidate based on the SwissADME and pkCSM analysis. Network pharmacology identified HSP90 as the primary target of amorphigenin, with a binding affinity of −11.11 kcal/mol. A molecular dynamic simulation study indicates stable binding conformation of amorphigenin–HSP90 complex with an average RMSD of 1.0 nm and lower RMSF value, and a significant amount of hydrogen bonds. The GMX_MMPBSA calculation reveals the binding energy of the complex to be −25 kcal/mol. Thus, our findings suggest that bioactive compounds of E. caudata , particularly amorphigenin, hold potential for the development of novel targeted therapies for cancer.