Target fishing de análogos beta-carbonílas com atividade anti-leishmanicida

Abstract

Leishmaniasis is still one of the most neglected diseases in the world, affecting underdeveloped and developing countries, due to the poor sanitary and socioeconomic conditions; 350 million people are considered at risk of contracting leishmaniasis according to the World Health Organization (WHO). However, one of the biggest challenges currently facing are treatments, which have been the same for over 50 years. The need to develop new therapies aimed at visceral leishmania (VL) becomes essential in this scenario. Combined with the need for new therapies, the use of in silico methods has gained significant notoriety in the planning of new drugs around the world, especially in the academic area, encouraging the pharmaceutical industry. Recently, Sankaranarayanan et al. synthesized 16 beta carboline alkaloids analogous compounds that demonstrated promising antiparasitic results in in vitro tests performed on cells infected with the amastigote and promastigote forms of the Leishmania infantum parasite. However, the researchers were unable to identify a possible biological target to test their potent inhibitors. With this, our work aimed to forecast a possible target using an inverted virtual screening method (target fishing). Analyzes converge to the target N-myristoyl transferase (PDB ID: 4BBH), which presented an active site with favorable occupation, electron π - electron π interactions with TYR 207 and hydrophobic interactions with VAL 71 of the compound, and added to that, its enzymatic structure has homologous compatibility with the genus Leishmania, which has a vital role in the parasitic life cycle. Besides, a study of all compounds was carried out, to clarify a possible structure-activity relationship (OER), in order to plan for potential new analogs of potentially active beta-carbonyl alkaloids.