Potential antichagasic agents: mutual prodrugs of hydroxymethylnitrofurazone and of nitric oxide releasing group

• Grant number: 09/06489-6
• Support Opportunities: Scholarships in Brazil - Master
• Start date: November 01, 2009
• End date: February 28, 2011
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Elizabeth Igne Ferreira
• Grantee: Ricardo Augusto Massarico Serafim
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Chagas disease is a pathology caused by Trypanosoma cruzi. Nowadays, 21 countries have been considered as endemic regions, where 28 million people live under the risk of being infected, 15 million people are infected and more than 41 thousands new cases are registered each ear. However, there are only two drugs available, nifurtimox and benznidazole, which show many side-effects. In Brazil, only the later has been used. This scarce therapeutic armamentarium against Chagas disease lead to the importance of searching for more effective chemotehrapeutic agents for its treatment. This said, the objective of this project comprehends the synthesis of dual activity compounds against T. cruzi, by means of the prodrug design, in which the active compounds are nitroheterocyclic derivative bioisosteres, that have been synthesized in our research group. The proposed derivatives are mutual prodrugs of hydroxymethyl nitrofurazone and of its bioisosteres, which have been promising as cruzain inhibitors, with groups that release nitric oxide. The resultant prodrugs can act by inhibiting cruzain and by cytotoxicity caused by the released nitric oxide. The compounds will be evaluated as enzyme inhibitors, and in epimastigotes/tripomastigotes and in macrophage and fibroblast toxicity assays. (AU)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

SERAFIM, Ricardo Augusto Massarico. Potential antichagasic agents: studies on mutual prodrug syntheses of hydroxymethylnitrofurazone bioisosteres and nitric oxide releasing group. 2011. Master's Dissertation - Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ) São Paulo.