Chemopreventive Potential of a Novel Epoxy-Sterol from Caryota urens L .: In Vitro NQO1 Assay and Integrated In Silico Docking, Analogues Simulation, and Molecular Dynamics

Objective Members of the Arecaceae family demonstrated potential to halt the progress of carcinogenesis by different mechanisms including induction of NAD(P)H:quinone oxidoreductase-1 (NQO1). However, the chemopreventive potential of the Caryota genus remains underexplored. The objective of the study is to Evaluate a bioactive compound isolated from Caryota urens for NQO1-mediated chemopreventive activity. Materials and Methods Petroleum ether leaf extract of C. urens was subjected to the isolation of a novel epoxy-sterol. Structural elucidation was performed using HR-MS, 1D, and 2D nuclear magnetic resonance (NMR) analyses. NQO1 induction was assayed using western blot (6.25 M to 100 M). In silico molecular docking into the KEAP-1 receptor protein data bank (PDB) (4IQK) against bromoflavone positive control, followed by molecular simulations comparing the sterol with seven structural analogues and molecular dynamics. Results The isolated epoxy-sterol was structurally confirmed and demonstrated significant upregulation of NQO1 expression (3.5 and 2.8 times that of the negative control at 100 μM and 25 μM, respectively) relative to the vehicle control. Docking studies revealed favourable binding interactions of the sterol (-8.781 kcal/mol) versus bromoflavone (-8.282 kcal/mol). Comparative analysis indicated competitive or superior binding behaviour relative to the seven analogues. Conclusion The epoxy-sterol from C. urens exhibits promising chemopreventive activity, highlighting its potential as a lead candidate for cancer chemoprevention drug development.