In vitro screening of 2-(1H-imidazol-1-yl)-1-phenylethanol derivatives as antiprotozoal agents and docking studies on Trypanosoma cruzi CYP51

Sterol 14a-demethylase (CYP51) is a key enzyme involved in the survival and virulence of many parasite protozoa, such as Trypanosoma and Leishmania species, thus representing a valuable drug target for the treatment of Kinetoplastid diseases. A set of azole-based compounds selected from an in-house compound library was in vitro screened against different human protozoan parasites. Several compounds showed selective activity against Trypanosoma cruzi, with compound 7 being the most active (IC50 40 nM). Given the structural similarity between the compounds here reported and known CYP51 inhibitors, a molecular docking study was performed to assess their binding with protozoal target and to rationalize the biological activity data.