Potent inhibitors of the enzyme sterol 14α-demethylase against Trypanosoma cruzi

Abstract

Chagas disease is a neglected tropical disease that affects more than 10 million people worldwide and threatens other 25 million who live in areas of risk. In this work, it is described how inhibitors of the enzyme 14α-demethylase (CYP51) were explored based in the piggyback approach, which is a strategy used to find new applications for known drugs or leads, in this case, against Trypanosoma cruzi. It is shown how the azole class acts in the inhibition of this target, which is a key in the process of ergosterol biosynthesis, a major sterol of the parasite. Their synthetic routes are described in detail and the relationship between the chemical structure of these molecules and the biological activity are correlated.