title: In vitro screening of 2-(1H-imidazol-1-yl)-1-phenylethanol derivatives as antiprotozoal agents and docking studies on Trypanosoma cruzi CYP51.
abstract: 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.
authors.affiliation: Department of "Chimica e Tecnologie del Farmaco", Sapienza University of Rome, Piazzale Aldo Moro, 5, 00185 Rome, Italy. Electronic address: daniela.devita@uniroma1.it.
authors.forename: Daniela
authors.initials: D
authors.lastname: De Vita
authors.affiliation: Department of "Biotecnologie, Chimica e Farmacia", "University of Siena", Via A. Moro 2, 53100 Siena, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Moraca
authors.affiliation: Department of "Biotecnologie, Chimica e Farmacia", "University of Siena", Via A. Moro 2, 53100 Siena, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Zamperini
authors.affiliation: Department of "Chimica e Tecnologie del Farmaco", Sapienza University of Rome, Piazzale Aldo Moro, 5, 00185 Rome, Italy.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Pandolfi
authors.affiliation: Department of "Chimica e Tecnologie del Farmaco", Sapienza University of Rome, Piazzale Aldo Moro, 5, 00185 Rome, Italy; "Istituto Pasteur-Fondazione Cenci Bolognetti", Department of "Chimica e Tecnologie del Farmaco", Sapienza University of Rome, Piazzale Aldo Moro, 5, 00185 Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Di Santo
authors.affiliation: Laboratory for Microbiology, Parasitology and Hygiene (LMPH), Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, Antwerp University, 2610 Antwerp, Belgium.
authors.forename: An
authors.initials: A
authors.lastname: Matheeussen
authors.affiliation: Laboratory for Microbiology, Parasitology and Hygiene (LMPH), Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, Antwerp University, 2610 Antwerp, Belgium.
authors.forename: Louis
authors.initials: L
authors.lastname: Maes
authors.affiliation: Department of "Chimica e Tecnologie del Farmaco", Sapienza University of Rome, Piazzale Aldo Moro, 5, 00185 Rome, Italy.
authors.forename: Silvano
authors.initials: S
authors.lastname: Tortorella
authors.affiliation: Department of "Chimica e Tecnologie del Farmaco", Sapienza University of Rome, Piazzale Aldo Moro, 5, 00185 Rome, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Scipione
mesh_terms: D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: C000612561:2-(1H-imidazol-1-yl)-1-phenylethanol; D000981:Antiprotozoal Agents; D007093:Imidazoles; D010626:Phenylethyl Alcohol
keywords: Azoles; CYP51; Trypanosoma cruzi