Targeting with structural analogs of natural products the purine salvage pathway in Leishmania (Leishmania) infantum by computer-aided drug design approaches

Abstract

Visceral Leishmaniasis (VL) has a high death rate with 500,000 new cases and 50,000 deaths occurring annually. Despite the development of novel strategies and technologies, there is no adequate treatment for the disease. Therefore, the purpose of this study is to find structural analogs of natural products as potential novel drugs to treat VL. To choose structural analogs from natural products that have demonstrated anti-leishmanial and anti-adenine phosphoribosyltransferase (APRT) properties, and that might bind with several targets from the purine salvage pathway, we used computer-aided drug design (CADD) techniques. Computational techniques were used to study the purine salvage pathway from Leishmania infantum, and molecular dynamic simulations were used to gather information on the interactions between ligands and proteins. An analog of the alkaloid Skimmianine, N,N-diethyl-4-methoxy-1-benzofuran-6-carboxamide, demonstrated a good binding affinity to two L. infantum targets, no expected toxicity, and potential for oral route administration. This study indicates that the compounds may have anti-leishmanial activity, which granted in vitro and in vivo experiments to settle this finding in the future.