Cruzain inhibition by hydroxymethylnitrofurazone and nitrofurazone: investigation of a new target in Trypanosoma cruzi

Author(s)

Trossini, Gustavo H. G. ^[1] ; Malvezzi, Alberto ^[2] ; T-do Amaral, Antonia ^[2] ; Rangel-Yagui, Carlota Oliveira ^[1] ; Izidoro, Mario A. ^[3] ; Cezari, Maria Helena S. ^[3] ; Juliano, Luiz ^[3] ; Chin, Chung Man ^[4] ; Menezes, Carla M. S. ^[1] ; Ferreira, Elizabeth Igne ^[1]

Affiliation

^[1] Univ Sao Paulo, Fac Ciencias Farmaceut, Dept Farm, BR-05508900 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Dept Quim Fundamental, Inst Quim, BR-05508900 Sao Paulo - Brazil

^[3] Univ Fed Sao Paulo, Escola Paulista Med, INFAR, Dept Biofis, Sao Paulo - Brazil

^[4] Univ Estadual Paulista, Fac Ciencias Farmaceut, Sao Paulo - Brazil

• Document type: Journal article
• Source: Journal of Enzyme Inhibition and Medicinal Chemistry; v. 25, n. 1, p. 62-67, FEB 2010.
• Web of Science Citations: 23

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 (IC(50)) for NF and NFOH presented values of 22.83 +/- 1.2 mu M and 10.55 +/- 0.81 mu M, respectively. AM1 semi-empirical molecular modeling studies were performed to understand the activity of the compounds, corroborating the observed cruzain inhibitory activity. (AU)

• FAPESP's process: 01/01192-3 - Potential antitripanosomal derived from nitro-heterocyclic compounds
• Grantee: Elizabeth Igne Ferreira
• Support Opportunities: Research Projects - Thematic Grants