Discovery of Polyphenolic Compounds from Mangifera indica as Potent Therapeutics for Strongyloides stercoralis Infection via Computer-aided Drug Design.

Abstract

Background: The global spread of Strongyloides stercoralis has escalated public health concerns, affecting over 600 million people worldwide. The rise in global migration has heightened the risk of transmission, underscoring the urgent need for effective treatment options.

Objective: This study aimed to investigate ten polyphenolic phytochemicals derived from Mangifera indica as potential alternatives to combat S. stercoralis.

Methods: The efficacy of these compounds was evaluated using computational techniques, including density functional theory (DFT) analysis, molecular docking, adsorption, distribution, metabolism, excretion, and toxicity (ADMET) assessment, and molecular dynamics (MD) simulations.

Results: DFT calculations revealed significant chemical reactivity in compounds such as kaempferol, ellagic acid, quercetin, norathyriol, mangiferin, and ferulic acid. Molecular docking identified mangiferin, quercetin, kaempferol, and norathyriol as top candidates for targeting S. stercoralis. A 200-ns MD simulation of the protein-ligand complex demonstrated the stability and binding behavior of these compounds compared to the reference drug, thiabendazole. ADMET screening confirmed their drug-likeness. Notably, quercetin and mangiferin exhibited strong binding affinities (ΔGbind = -42.35 and -54.57 kcal/mol, respectively), outperforming thiabendazole (ΔGbind = -28.94 kcal/mol).

Conclusion: Quercetin and mangiferin emerge as promising alternatives to thiabendazole, offering favorable chemical reactivity, potent inhibition constants, and strong biological activity for the treatment of S. stercoralis.