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Study of antimalarial potential substances in Plasmodium falciparum "in vitro" and experimental malaria by Plasmodium berghei in mice

Grant number: 09/53267-9
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): January 01, 2010
Effective date (End): September 30, 2013
Field of knowledge:Biological Sciences - Parasitology
Principal Investigator:Alejandro Miguel Katzin
Grantee:Alexandre Yukio Saito
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Worldwide malaria kills over one million people per year, mostly children, one of the most important infectious diseases and a major public health problem, especially for the underdeveloped and developing countries. With the emergence of resistant strains new targets and therapeutic treatments are needed. The studies developed in our laboratory on the biosynthesis of isoprenoids intraeritrocíticas forms of Plasmodium falciparum "in vitro" was demonstrated that the parasite has an active route for the biosynthesis of isoprenoids using the 2-C-methyl-D-erythritol-4-phosphate (MEP) from pyruvate and glyceraldehyde-3-phosphate and that it is able to synthesize some vitamins. From these studies, substances that inhibit biosynthesis of isoprenoids have been studied and they have been showing antimalarial activity, along with its results some doubts about the role of vitamins synthesized by the parasite have emerged. The main question is the involvement of carotenoids in the antioxidant defense during infection by P. falciparum, we obtained some preliminary results, though other approaches are needed to prove our hypothesis. According to the results obtained in our laboratory, we believe that the route of isoprenoids may be a potential target for the development of new antimalarial drugs including some herbicides. And for this reason studies "in vivo" and "in vitro" for toxicity and genotoxicity induced or not by new chemotherapeutic agents are needed. Our objectives in this project researching the effects of inhibitors of various products in the biosynthesis of isoprenoids with antimalarial activity in Plasmodium falciparum "in vitro" and in experimental malaria caused by Plasmodium berghei in mice and study the profile of oxidative stress in plasma and red blood cells during infection. (AU)