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Evaluation of possible inhibitors of prenylquinones and prenylated fatty acid biosynthesis in the intraerythrocytic stages of Plasmodium falciparum

Grant number: 16/13948-0
Support type:Scholarships in Brazil - Master
Effective date (Start): October 01, 2016
Effective date (End): September 30, 2018
Field of knowledge:Biological Sciences - Biochemistry - Biochemistry of Microorganisms
Principal researcher:Alejandro Miguel Katzin
Grantee:Ignasi Bofill Verdaguer
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Malignant tertian malaria is a human disease caused by the Plasmodium falciparum parasite. The World Health Organization estimated that in 2015 from 149 million to 303 million people were affected by malaria,from which approximately 438,000 died. Most deaths occur in children and pregnant women. A resistance has already emerged to drugs currently being used. As a result of this it is necessary to find targets for the development of new antimalarial drugs.The study of essential pathways for the parasite that are absent in the vertebrate host is a strategy for the development of new drugs. After the demonstration of the isoprenoid biosynthesis pathway using 2-C-methyl-D-erythritol-4-phosphate (MEP) in P. falciparum, our laboratory has been studying various routes of biosynthesis of secondary isoprenic compounds as a potential target for the treatment of the disease. Through this, our group was able to identify several prenilquinonas in Plasmodium falciparum as tocopherol, menaquinone, ubiquinone and the evidence of the presence of phylloquinone is emerging. It is reasonable to think that an inhibition of the biosynthesis of these substances could affect the development of the parasite. In fact, some compounds that alter the biosynthesis of different isoprenic compounds have been successfully tested in Plasmodium.In this study, we hope to evaluate the antimalarial effect on Plasmodium falciparum cultures of new drugs that we think may inhibit prenYlquinonas synthesis or prenylated fatty acids. (AU)

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