A computational study to identify the metabolites in Lippia alba capable of inhibiting gastric cancer through BCL-2 protein inhibition Scientific paper

Abstract

In this study, a computational analysis was performed to evaluate the therapeutic potential of 73 compounds from Lippia alba as candidates for gas­tric cancer treatment. Most compounds exhibited low toxicity, except for 4-meth­yl­pent-2-enolide and β-acorenol, which demonstrated significant toxic effects. Molecular docking studies revealed that (Z)-nerolidol and 13-hydroxy-valen­cene both bind to the BCL2 protein, a key regulator of apoptosis in cancer cells. Furthermore, ADMET analysis predicted that both compounds are non-toxic. Molecular dynamics simulations showed that only (Z)-nerolidol main­tained a stable interaction with domain 4 of BCL2, specifically with the critical Lys17 residue, which is essential for BCL2’s inhibitory function. QM/MM cal­culations confirmed the formation of hydrogen bonds between (Z)-nerolidol and Lys17, Ile14 and Ser49, with an estimated binding energy of –62.47 kJ mol^-1, suggesting a stable protein–ligand complex. These findings support the potential of (Z)-nerolidol as a lead compound for BCL2 inhibition and high­light its promise as a novel therapeutic agent for gastric cancer.