Browsing by Author "Mugwabi, Musa"

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    Antimalarial mechanism of action of compounds from zanthoxylum species : an in-silico study.
    (Busitema University, 2026) Mugwabi, Musa
    Malaria remains a critical global health crisis exacerbated by emerging drug-resistant strains of Plasmodium falciparum. This study investigated the multi-target antimalarial mechanisms of phytochemicals derived from the genus Zanthoxylum using an integrated computational framework. A comprehensive database of 251 Zanthoxylum-derived compounds was constructed and subjected to Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) screening via SwissADME. Out of these, the majority of the small alkaloids exhibited favorable drug-likeness parameters with zero Lipinski rule violations. Ligand-based target prediction using SwissTargetPrediction identified 1,047 potential compound targets which were intersected with 108 malaria-associated disease genes from GeneCards, DisGeNET and OMIM yielding 22 high-confidence overlapping targets. Network topology analysis in Cytoscape revealed central immune-modulatory and pathogenesis hubs notably Tumor Necrosis Factor (TNF, degree = 18), Toll-like Receptor 4 (TLR4, degree = 15) and Intercellular Adhesion Molecule 1 (ICAM1, degree = 14). Molecular docking executed via AutoDock Vina within the PyRx interface validated strong binding interactions against prioritized targets. Indoleamine 2,3-Dioxygenase 1 (IDO1, PDB: 5ETW) demonstrated exceptional binding affinities with lead compound cpd_53 at –10.7 kcal/mol and cpd_3 at –10.5 kcal/mol, stabilized by continuous pi-pi stacking interactions with the core heme cofactor. ICAM1 (PDB: 1P53) displayed moderate binding, led by cpd_3 at –7.8 kcal/mol. These findings elucidate a multi-target mechanism spanning direct antiparasitic action, host immune modulation and infection blocking positioning Zanthoxylum alkaloids as excellent putative lead scaffolds for downstream in vitro validation.