Cruzain inhibition by hydroxymethylnitrofurazone and nitrofurazone: investigation of a new target in Trypanosoma cruzi.
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.
Trossini
Gustavo H G
GH
Departamento de Farmácia, Faculdade de Ciências Farmacêuticas, USP, São Paulo, Brazil. trossini@usp.br
Malvezzi
Alberto
A
T-do Amaral
Antonia
A
Rangel-Yagui
Carlota Oliveira
CO
Izidoro
Mario A
MA
Cezari
Maria Helena S
MH
Juliano
Luiz
L
Chin
Chung Man
CM
Menezes
Carla M S
CM
Ferreira
Elizabeth Igne
EI
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
D015853:Cysteine Proteinase Inhibitors; D015800:Protozoan Proteins; D014344:Trypanocidal Agents; C483719:hydroxymethylnitrofurazone; D003546:Cysteine Endopeptidases; C074032:cruzain, Trypanosoma cruzi; D009583:Nitrofurazone