In silico studies on complete inhibition of Trypanothione reductase of Leishmania infantum by γ-sitosterol and antcin-A: Novel target for anti-leishmanial activity

Abstract

Inhibition of the trypanothione reductase (Try R) activity interaction has been becomes a new therapeutic strategy to leishmaniasis. Trypanothione reductase is a genetically validated drug target enzyme for structure-based drug design against Leishmania, the causative agent of human trypanosomiasis. We used theoretical docking study, conducted on a sample previously reported for anti-cancer, anti-diabetic and antioxidant potential of Kaempferol, guggultetrol, γ-sitosterol and antcin-A at the binding site of Leishmania infantum trypanothione reductase (Try R) examine interaction energy. These studies indicate that γ-sitosterol and antcin-A displays potent activity against Try R with lowest binding energy and RMSD values to be -9.34 kcal mol-1 for γ-sitosterol,-8.36 Kcal mol-1 for antcin-A and 2.0 Å. Docking analysis of Try R with ligands enabled us to identify specific residues viz., Pro-59, Ala-200, Ala-205, Glu-203, Lue-62, Asp-218, Val-64, Cys-193 and Gln-280 within the TryR and Val-58, Leu-95, Ala-181, Val-201, Ile-206, Asn-266, Asp-277 and Met-282 binding pocket to play an important role in ligand binding affinity. The results of our study contributes towards the development of novel therapeutics based on trypanothione reductase inhibition. © 2013 Academic Journals Inc.