Fluorescence Spectroscopy Reveals Resveratrol Binding to a Hydrophobic Pocket in Leishmania amazonensis Sir2-Related...

Resveratrol, a natural phytoalexin synthesized by certain plants in response to injury, exhibits antimicrobial properties and various medically significant effects, including anticancer and antiaging activities. Although its exact mechanism of action is still under investigation, it is believed to involve its interaction with a group of protein deacetylases known as sirtuins. Sirtuins are crucial in regulating metabolism, stress responses, and processes such as lifespan extension through caloric restriction. In this study, we report the inhibitory effect of resveratrol on the growth of Leishmania amazonensis promastigotes, highlighting its potential as a microbicide. Through fluorescence spectroscopy assays and in silico analysis, we identified and characterized the interaction between resveratrol and Sir2-related protein 1 from L. amazonensis (rLaSir2RP1). Our results demonstrate a direct interaction between resveratrol and rLaSir2RP1, characterized by a binding constant of 10⁵ M^-1. This interaction involves a single binding site located near a hydrophobic pocket, which includes its solely tryptophan residue.