Molecular Docking Studies on Eudesmane Sesquiterpenes as Potential Anti-leishmanial Agents

Abstract

In this study, potential inhibitors against Leishmania were identified by docking

30 bioactive compounds from the methanol extract of Solanum erianthum leaves with key Leishmania protein targets. Among the screened compounds, six demonstrated strong binding affinities, with docking scores ranging from −9.2 to −11.4 kcal/mol, particularly against enzymes like trypanothione reductase and arginase, which are crucial for Leishmania’s survival. Experimental validation using in vitro assays confirmed the inhibitory activity of the top three compounds, showing IC50 values between 10 to 25 µM. The findings suggest that compounds from Solanum erianthum have the potential to act as lead inhibitors for Leishmania proteins, especially with binding affinity values 30–50% higher than standard inhibitors. Further experimental tests, including enzyme inhibition assays and Leishmania-infected animal models, will be conducted to evaluate their in vivo efficacy. Lead optimization, including structural modifications, is recommended to enhance potency, with a focus on improving pharmacokinetic properties. Visual representations, including protein-ligand interaction diagrams, demonstrated strong hydrogen bonding and hydrophobic interactions, which are critical for the compounds' inhibitory effects.