Abstract

Aim: To study a new series of [1,2,3] triazolo[1,5-alpha] pyridine derivatives as trypanocidal agents because current antichagasic pharmacologic therapy is only partially effective. Materials & methods: The effect of the series upon Trypanosoma cruzi epimastigotes and murine macrophages viability, cell cycle, cell death and on the metabolites of the sterol biosynthesis pathway was measured; also, docking in 14 alpha-demethylase was analyzed. Results: Compound 16 inhibits 14 alpha-demethylase producing an imbalance in the cholesterol/ergosterol synthesis pathway, as suggested by a metabolic control and theoretical docking analysis. Consequently, it prevented cell proliferation, stopping the cellular cycle at the G2/M phase, inducing cell death. Conclusion: Although the exact cell death mechanism remained elusive, this series can be used for the further rational design of novel antiparasitic molecules.