In silico screening based on chemoinformatics and molecular docking of trypanothione reductase inhibitors from Trypanosoma cruzi

Abstract

Chagas disease is caused by the parasite Trypanosoma cruzi. One of the two first-line drugs for treatment is nifurtimox, a nitrofuran that exhibits high toxicity. Therefore, the need arises to investigate new therapeutic options, and, in this sense, our objective was to study compounds that maintain the trypanocidal activity associated with the furan nucleus and by structural modification of substituents reduce their toxicity. In the following research work, a chemical library was formed using the databases PubChem, ChEMBL and ChemSpider, later a virtual screening was carried out with the chemoinformatic tools Way2Drug, molinspiration, DataWarrior and admetSAR obtaining the prediction of biological activity, physicochemical parameters, data of toxicity and pharmacokinetic properties, respectively. The last stage consisted of the molecular docking of the molecules at the active site of the trypanothione reductase protein of Trypanosoma cruzi, determining its binding energy and intermolecular interactions. Compounds NF-85, NF-150, NF-246 and NF-279 with potential anti-T. cruzi activity were identified, the four molecules had greater affinity for trypanothione reductase (-7.0, -7.2, -7.0 and -7.3 kcal / mol, respectively), compared to nifurtimox (-6.7 kcal / mol).