Abstract

Background: Cancer pain remains a significant challenge in palliative care, often necessitating opioid use despite risks of addiction and adverse effects. Leveraging ethnomedicinal knowledge, this study explores the therapeutic potential of Mitragyna speciosa and Garua pinata derivatives as opioid receptor-targeted therapies for cancer pain management. The study aims to identify bioactive compounds with strong binding affinities to opioid receptors, evaluate their pharmacokinetics, and compare their safety and efficacy to conventional opioids.
Methods: An In-silico approach was employed to investigate the binding affinities of bioactive compounds, including Mitragynine, 7-Hydroxymitragynine, and 6-Hydroxygaruanin-V, to mu (μ), kappa (κ), and delta (δ) opioid receptors. Binding stability was assessed through RMSD analysis, while pharmacokinetic parameters, including molecular weight, ADMET properties, and toxicity, were analyzed to predict drug-likeness and safety.
Results: Docking simulations revealed that Mitragynine, 7-Hydroxymitragynine, and 6-Hydroxygaruanin-V exhibit high binding affinities toward opioid receptors. Notably, 7-Hydroxymitragynine demonstrated a binding affinity to the muopioid receptor comparable to morphine. The compounds exhibited favorable pharmacokinetic profiles, low predicted toxicity, and potential for enhanced receptor interactions through redox-driven mechanisms.
Conclusion: Mitragyna speciosa and Garua pinata derivatives exhibit strong potential as opioid receptor-targeted therapies for cancer palliative care. With promising receptor-binding profiles, superior pharmacokinetics, and low toxicity, these compounds may serve as safer alternatives to traditional opioids. Further in-vitro and in-vivo studies are warranted to validate their clinical efficacy for cancer pain relief.

Key words: Ethnomedicine, phytochemicals, molecular docking, protein interaction, opioid receptor