Browsing by Author "Mukembo, Thomas"

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    Molecular docking of vernonia amygdalina del compounds against malaria enzymes.
    (Busitema University, 2026) Mukembo, Thomas
    Malaria remains one of the leading causes of morbidity and mortality worldwide, with increasing resistance to artemisinin-based combination therapies driving the search for new antimalarial leads from natural sources. Vernonia amygdalina (VA), a plant long used in traditional medicine to manage malaria and its associated symptoms, contains a diverse array of phytochemicals whose molecular interactions with malaria-associated targets remain incompletely characterized. This study employed an integrated network pharmacology and molecular docking approach to evaluate the antimalarial potential of bioactive compounds from V. amygdalina. From an initial library of 348 phytochemicals reported in the literature, compounds satisfying Lipinski's rule of five were retained for further analysis, and SwissTargetPrediction was used to identify their putative protein targets. Intersection of these compound targets with malaria-associated disease genes, followed by protein–protein interaction network analysis, identified TNF, TLR4 and IL1B as the most druggable core targets. Molecular docking of the VA compound library against these three targets (PDB: 2AZ5, 4G8A and 8RYK) was performed using AutoDock Vina in PyRx. Docking results showed markedly weaker binding to TNF (best affinity −7.0 kcal/mol, mean −3.6 kcal/mol) compared with TLR4 (best affinity −9.6 kcal/mol, mean −6.4 kcal/mol; 29 compounds at or below −8.0 kcal/mol) and IL1B (best affinity −9.0 kcal/mol, mean −6.3 kcal/mol; 21 compounds at or below −8.0 kcal/mol). Apigenin-7-O-β-D-glucoside, Veramyoside I, Vernonioside D1 and Vernoamyoside C1 emerged as the most consistent multi-target binders across all three proteins. These findings provide computational, mechanistic support for the traditional use of V. amygdalina in malariamanagement, particularly through modulation of TLR4- and IL1B-mediated inflammatory pathways, and identify several phytochemicals as promising candidates for further in vitro and in vivo antimalarial validation.