title: Cruzain inhibition by hydroxymethylnitrofurazone and nitrofurazone: investigation of a new target in Trypanosoma cruzi.
abstract: Nitrofurazone (NF) and its derivative, hydroxymethylnitrofurazone (NFOH), have presented antichagasic activity. NFOH has higher activity and lower mutagenicity. The aim of this work was to assess whether NF and its derivative NFOH would also be inhibitors of cruzain, besides their trypanothione reductase inhibitory activity. In vitro cruzain inhibition tests were performed for both compounds, and the 50% inhibitory concentration (IC50) for NF and NFOH presented values of 22.83 +/- 1.2 microM and 10.55 +/- 0.81 microM, respectively. AM1 semi-empirical molecular modeling studies were performed to understand the activity of the compounds, corroborating the observed cruzain inhibitory activity.
authors.affiliation: Departamento de Farmácia, Faculdade de Ciências Farmacêuticas, USP, São Paulo, Brazil. trossini@usp.br
authors.forename: Gustavo H G
authors.initials: GH
authors.lastname: Trossini
authors.forename: Alberto
authors.initials: A
authors.lastname: Malvezzi
authors.forename: Antonia
authors.initials: A
authors.lastname: T-do Amaral
authors.forename: Carlota Oliveira
authors.initials: CO
authors.lastname: Rangel-Yagui
authors.forename: Mario A
authors.initials: MA
authors.lastname: Izidoro
authors.forename: Maria Helena S
authors.initials: MH
authors.lastname: Cezari
authors.forename: Luiz
authors.initials: L
authors.lastname: Juliano
authors.forename: Chung Man
authors.initials: CM
authors.lastname: Chin
authors.forename: Carla M S
authors.initials: CM
authors.lastname: Menezes
authors.forename: Elizabeth Igne
authors.initials: EI
authors.lastname: Ferreira
mesh_terms: D000818:Animals; D003546:Cysteine Endopeptidases; D015853:Cysteine Proteinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009583:Nitrofurazone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors*; D014344:Trypanocidal Agents / Q000737:chemistry / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000201:enzymology
chemical_list: D015853:Cysteine Proteinase Inhibitors; D015800:Protozoan Proteins; D014344:Trypanocidal Agents; C483719:hydroxymethylnitrofurazone; D003546:Cysteine Endopeptidases; C074032:cruzain, Trypanosoma cruzi; D009583:Nitrofurazone