A computational study to identify the metabolites in Lippia alba capable of inhibiting gastric cancer through BCL-2 protein inhibition
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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.
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This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution license 4.0 that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
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Laboratorio Nacional de Supercómputo del Sureste de Mexico
Grant numbers 202501011N -
Consejo Nacional de Ciencia y Tecnología, Guatemala
Grant numbers CONACyT 123732
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