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

• DOI: 10.1016/j.ejmech.2016.02.028
• Publication Date: 2016-02-15T19:24:43Z
• Authors: Daniela De Vita; Francesca Moraca; Claudio Zamperini; Fabiana Pandolfi; Roberto Di Santo; An Matheeussen; Louis Maes; Silvano Tortorella; Luigi Scipione
• Keywords: 0303 health sciences; Dose-Response Relationship, Drug; Molecular Structure; Trypanosoma cruzi; Antiprotozoal Agents; Drug Evaluation, Preclinical; Imidazoles; Azoles; CYP51; Trypanosoma cruzi; Drug Discovery3003 Pharmaceutical Science; Organic Chemistry; Pharmacology; Fibroblasts; Phenylethyl Alcohol; Cell Line; 3. Good health; Molecular Docking Simulation; Structure-Activity Relationship; 03 medical and health sciences; Parasitic Sensitivity Tests; Humans

Sterol 14α-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.