Análisis estructural de interacciones in silico de fitoconstituyentes de Solanum americanum, Solanum guaraniticum y Solanum lycopersicum con la proteína tripanotiona reductasa de Leishmania infantum

Abstract

Leishmania infantum is the main cause of visceral leishmaniasis in humans and several other mammals. Numerous studies suggest that trypanothione reductase (TR) is a good target to search for bioactive molecules capable of interacting and inhibiting functions of this protein. The objective of this research was to determine in silico phytoconstituents from Solanum americanum, Solanum guaraniticum and Solanum lycopersicum that show interaction affinities to TR, by analysis of molecular docking and molecular dynamics simulations. A total of thirty molecules described in S. americanum, S. guaraniticum, and S. lycopersicum were evaluated. Molecular docking tests were performed between these molecules and TR’s active site. All molecules demonstrated
interaction affinities to TR; however, the ones which showed significantly favorable interaction energy values (p<0.001) were solasodine, solamargine, and manghaslin. Subsequently, the analysis of molecular dynamics simulations revealed that only the interaction with solasodine proved to be stable and present significantly favorable interaction-free energy (ΔGu = -4.68±2.57 kcal.mol-1; p<0.05); however, interactions with solamargine and manghaslin were unfavorable (ΔGu = 0.87±0.19 kcal.mol-1 and ΔGu = 12.79±9.25 kcal.mol-1 respectively). The active residues of TR involved in the interaction with solasodine were Lys60, Tyr198 and Arg287. These findings suggest that the TR protein could be an interaction target for the glycoalkaloid solasodine , and could be a potential inhibitor of its enzymatic activity.