Planejamento de novos inibidores da CYP51 do Trypanosoma Cruzi por estudos de QSAR

Abstract

Chagas disease kills over 10,000 people per year and approximately 8 million people are infected by Trypanosoma cruzi. The reference drug for treatment of the disease, benznidazole, is the same since the 70s. In recent years, many CYP51 inhibitors were tested against this parasite’s target. One of them, posaconazole, was even tested in clinical trials that unfortunately could not prove a superior efficiency compared to benznidazole. Nevertheless, there are still many evidences that CYP51 is a great potential target to treat T. cruzi infection. The research for new effective molecules that can cure the chronic phase of the disease is essential. 2D and 3DQuantitative Structure Activity Relationship (QSAR) studies were conducted in this work to create three QSAR models using the chemical structures of 197 pyrydine and azole published compounds that already went through either in vivo or in vitro tests. After the analysis of the models, new analogues not yet synthesized were suggested here and had their biological activity and synthetic availability assessed.