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Structural characterization of vitamin B1 and B6 synthesis pathway enzymes in Plasmodium falciparum and Mycobacterium tuberculosis

Grant number: 18/21213-6
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): January 01, 2019
Effective date (End): February 28, 2022
Field of knowledge:Biological Sciences - Biophysics
Principal Investigator:Alessandro Silva Nascimento
Grantee:Angélica Luana Carrillo Barra
Home Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
Associated research grant:15/26722-8 - Drug discovery against human infectious diseases, AP.TEM

Abstract

Infectious diseases are a threat to humanity and currently its pathogens are spreading geographically due to globalization and the development of drug resistance available. The drug resistance currently available is occurring in almost all pathogens and therefore there is an urgent need to discover new therapeutic targets and/or new target classes. In this project the focus will be on the discovery of new prodrugs exploring the biosynthesis pathways of B1/B6 vitamins of human pathogens: Plasmodium falciparum, the parasite responsible for causing severe Malaria in addition to the responsible for Tuberculosis, Mycobacterium tuberculosis. For the design of compounds, the crystallographic structures of the respective enzymes involved in the biosynthesis of vitamins B1/B6 will be determined, aiming the incorporation of the compounds in the metabolism of the pathogen. Therefore the new compounds will seek to poison the vitamin-dependent enzymes as cofactors. (AU)