In Silico Screening of

Leishmaniasis remains a major neglected tropical disease with limited therapeutic options, increasing drug resistance, and significant treatment-associated toxicity. Ornithine decarboxylase (ODC), which plays an essential role in polyamine synthesis and survival of parasites, is a potential molecular target for the discovery of anti-leishmanial agents. In this study, 49 natural products with bioactive properties, such as cannabinoids, terpenoids, flavonoids, polyphenols, and alkaloids, are evaluated against ODC using computational approaches like molecular docking and molecular dynamics (MD) simulations. During molecular docking analysis, some compounds showed good affinity binding to the ODC catalytic site, namely Sanguinarine (-8.53 kcal/mol), Rutin (-8.15 kcal/mol), Evodiamine (-7.83 kcal/mol), Cannabinol (-7.58 kcal/mol), and β-sitosterol (-7.56 kcal/mol). Analysis of protein-ligand complex interactions showed that these compounds formed hydrogen bonds, hydrophobic interactions, π-alkyl contacts, π-cation contacts, and van der Waals forces in the vicinity of the active-site amino acid residue. For further analysis, MD simulations were performed for 100 ns on the best-docking complexes. Comparative trajectory analysis of RMSD, RMSF, Rg, SASA, and hydrogen bonds was conducted, revealing that Rutin and Evodiamine exhibited relatively high structural stability and consistent interactions within the ODC binding cavity. Overall, this study indicates that the natural compounds analyzed here could be considered promising hit compounds for anti-leishmanial drug discovery against ODC. However, further investigations using experimental techniques are required to confirm their biological properties and efficacy.