Insights about resveratrol analogs against trypanothione reductase of <i>Leishmania braziliensis</i>: Molecular modeling, computational docking and <i>in vitro</i> antileishmanial studies

In this work, we combined molecular modeling, computational docking and <i>in vitro</i> analysis to explore the antileishmanial effect of some resveratrol analogs (ResAn), focusing on their pro-oxidant effect. The molecular target was the trypanothione reductase of <i>Leishmania braziliensis</i> (LbTryR), an essential component of the antioxidant defenses in trypanosomatid parasites. Three-dimensional structures of LbTryR were modeled and molecular docking studies of ResAn1-5 compounds showed the following affinity: ResAn1 &gt; ResAn2 &gt; ResAn4 &gt; ResAn5 &gt; ResAn3. Positive correlation was observed between these compounds’ affinity to the LbTryR and the IC₅₀ values against <i>Leishmania sp</i> (ResAn1 L. braziliensis promastigotes treated, ResAn1 probably occupies NS interfering in the electron transfer processes responsible for the catalytic reaction. The <i>in silico</i> prediction of ADMET properties suggests that ResAn1 may be a promising drug candidate with properties to cross biological membranes and high gastrointestinal absorption, not violating Lipinski’s rules. Ultimately, the antileishmanial effect of ResAn can be associated with a pro-oxidant effect which, in turn, can be exploited as an antimicrobial agent. Communicated by Ramaswamy H. Sarma