title: Targeting CYP51 for drug design by the contributions of molecular modeling.
abstract: CYP51 is an enzyme of sterol biosynthesis pathway present in animals, plants, protozoa and fungi. This enzyme is described as an important drug target that is still of interest. Therefore, in this work, we reviewed the structure and function of CYP51 and explored the molecular modeling approaches for the development of new antifungal and antiprotozoans that target this enzyme. Crystallographic structures of CYP51 of some organisms have already been described in the literature, which enable the construction of homology models of other organisms' enzymes and molecular docking studies of new ligands. The binding mode and interactions of some new series of azoles with antifungal or antiprotozoan activities has been studied and showed important residues of the active site. Molecular modeling is an important tool to be explored for the discovery and optimization of CYP51 inhibitors with better activities, pharmacokinetics, and toxicological profiles.
authors.affiliation: Laboratório de Modelagem Molecular e Pesquisa em Ciências Farmacêuticas (LAMCIFAR), Universidade Federal do Rio de Janeiro, Campus Macaé Professor Aloísio Teixeira, Avenida São José do Barreto 767, CEP 27965-045, Macaé, RJ, Brazil.
authors.forename: Vitor W
authors.initials: VW
authors.lastname: Rabelo
authors.affiliation: Laboratório de Modelagem Molecular e Pesquisa em Ciências Farmacêuticas (LAMCIFAR), Universidade Federal do Rio de Janeiro, Campus Macaé Professor Aloísio Teixeira, Avenida São José do Barreto 767, CEP 27965-045, Macaé, RJ, Brazil.
authors.forename: Taísa F
authors.initials: TF
authors.lastname: Santos
authors.affiliation: Laboratório de Antibióticos, Bioquímica, Ensino e Modelagem Molecular (LabiEMol), Instituto de Biologia, Universidade Federal Fluminense, Campus Valonguinho Outeiro de São João Baptista s/n, Centro, CEP 24210130, Niterói, RJ, Brazil.
authors.forename: Luciana
authors.initials: L
authors.lastname: Terra
authors.affiliation: Laboratório de Antibióticos, Bioquímica, Ensino e Modelagem Molecular (LabiEMol), Instituto de Biologia, Universidade Federal Fluminense, Campus Valonguinho Outeiro de São João Baptista s/n, Centro, CEP 24210130, Niterói, RJ, Brazil.
authors.forename: Marcos V
authors.initials: MV
authors.lastname: Santana
authors.affiliation: Laboratório de Antibióticos, Bioquímica, Ensino e Modelagem Molecular (LabiEMol), Instituto de Biologia, Universidade Federal Fluminense, Campus Valonguinho Outeiro de São João Baptista s/n, Centro, CEP 24210130, Niterói, RJ, Brazil.
authors.forename: Helena C
authors.initials: HC
authors.lastname: Castro
authors.affiliation: Laboratório de Modelagem Molecular e QSAR (ModMolQSAR), Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, 373, Cidade Universitária, CEP 21941-599, Rio de Janeiro, RJ, Brazil.
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Rodrigues
authors.affiliation: Laboratório de Modelagem Molecular e Pesquisa em Ciências Farmacêuticas (LAMCIFAR), Universidade Federal do Rio de Janeiro, Campus Macaé Professor Aloísio Teixeira, Avenida São José do Barreto 767, CEP 27965-045, Macaé, RJ, Brazil.
authors.forename: Paula A
authors.initials: PA
authors.lastname: Abreu
mesh_terms: D058888:14-alpha Demethylase Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D001665:Binding Sites; D015195:Drug Design; D006801:Humans; D062105:Molecular Docking Simulation; D009181:Mycoses / Q000188:drug therapy / Q000201:enzymology / Q000382:microbiology; D011485:Protein Binding; D017433:Protein Structure, Secondary; D011528:Protozoan Infections / Q000188:drug therapy / Q000201:enzymology / Q000469:parasitology; D058886:Sterol 14-Demethylase / Q000096:biosynthesis / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D058888:14-alpha Demethylase Inhibitors; D000935:Antifungal Agents; D000981:Antiprotozoal Agents; D058886:Sterol 14-Demethylase
keywords: CYP51; antifungal; antiprotozoan; drug design; molecular modeling