In Silico Assessment of the ADMET Properties of 7-Hydroxymitragynine and its Interaction with Human Serum Albumin and 1-Acid Glycoprotein

Mitragyna speciosa (kratom) is a psychoactive plant native to Southeast Asia that is traditionally used for pain relief, increased physical endurance, and as a muscle relaxant. Its most potent alkaloid, 7-hydroxymitragynine (7-OH-MTG), acts on the µ-opioid receptor, providing analgesic effects. Assessment of its drug-likeness and ADMET properties indicates the suitability of 7-OH-MTG as a drug with favorable pharmacokinetic profile. Further, characterization of its interaction with plasma transport proteins such as human serum albumin (HSA) and α1-acid glycoprotein (AAG) is vital for assessing its therapeutic potential. Molecular docking suggests preferential binding of 7-OH-MTG to site III on subdomain IB of HSA and the central binding pocket of both variants F1*S and A of AAG. The involvement of various hydrophobic interactions (alkyl, pi-alkyl, pi-pi), hydrogen bonds, and van der Waals forces are suggested in stabilizing the 7-OH-MTG–protein complexes. MD simulation results supported the overall stable nature of the binding of 7-OH-MTG to both proteins based on several parameters, including root-mean-square deviation (RMSD), total energy, root-mean-square fluctuation (RMSF), radius of gyration (Rg), and solvent accessible surface area (SASA). These findings have clear significance in the development of potential therapeutic agents derived from kratom.