Molecular Docking And In Silico Analysis Of Parkia Biglobosa Bioactive Compounds For Inhibition Of Acetylcholinesterase And L-Amino Acid Oxidase In Snake Venom-Induced Systemic Toxicity

Snakebite envenoming is a significant neglected tropical disease with a high mortality and morbidity burden, especially in resource-constrained areas, in which the systemic toxicity is mediated by enzymes like acetylcholinesterase (AChE) and L-amino acid oxidase (LAAO). Despite the ethnomedicinal use of Parkia biglobosa in managing envenomation, its bioactive constituents lack detailed molecular-level validation and integrated pharmacokinetic characterisation. This study investigated the inhibitory potential of selected P. biglobosa phytochemicals against AChE and LAAO using an integrative molecular docking and in silico pharmacokinetic approach. Eight bioactive compounds were selected from the plant, while edrophonium and aristolochic acid were used as control inhibitors in this study. The 3D structures of the bioactive compounds and the control inhibitors were retrieved from the PubChem database. Additionally, the crystal structures of acetylcholinesterase (4QWW) and L-amino acid oxidase (5Z2G) were obtained from the Protein Data Bank (PDB). Using the RDKit cheminformatics package, the drug-likeness of the bioactive compounds was assessed, and AutoDock Vina was employed for molecular docking with the target proteins. The docked complexes were analysed with BIOVIA Discovery Studio Visualizer. Additionally, the Mordred and RDKit libraries were used to identify the ADMET properties of the ligands. Quercetin and luteolin were the best candidates with desirable binding affinities, with quercetin strongly binding AChE (−9.9 kcal/mol; Ki ≈ 0.06 μM) outperforming the reference inhibitor edrophonium, and luteolin displaying a competitive affinity towards LAAO (−9.5 kcal/mol; Ki ≈ 0.11 μM). Each of the lead compounds met Lipinski requirements, exhibited high predicted gastrointestinal absorption and acceptable toxicity profiles. These results imply that flavonoid scaffolds of P. biglobosa might engage with important catalytic sites in both enzymes, and thereby may mediate neurotoxic and cytotoxic pathways of envenomation, which are molecular-level-supported indicators of the ethnopharmacological significance of P. biglobosa, and may be useful as a complement to antivenom therapy in snakebite envenomation. Further, molecular dynamics, in vitro and in vivo studies are required to validate these results.