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

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 ?-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.