Synthesis of a library of benzothiazolinic derivatives for the evaluation of inhibition of Leishmania major dihydroorotate dehydrogenase

• Grant number: 18/10418-6
• Support type: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): September 01, 2018
• Effective date (End): November 30, 2019
• Field of knowledge: Health Sciences - Pharmacy
• Principal researcher: Flavio da Silva Emery
• Grantee: Letícia Bueno de Oliveira
• Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated scholarship(s): 19/01173-2 - Targeting cancer metastasis through isoform selective HDAC inhibitors, BE.EP.IC

Abstract

Neglected tropical diseases (NTDs) caused by infectious agents, such as parasites, are endemic to low-income populations, and kill or incapacitate millions of people. These diseases have unacceptable indicators and reduced investments in research, production of medicines and inefficient control. An important parameter in the development of new treatments for NTDs is the study of parasite-specific metabolic pathways, which are excellent targets for drugs, but this still is under explored. Among these metabolic pathways, a dihydroorotate dehydrogenase enzyme (DHODH), which catalyzes the oxidation of dihydroorotate to orotare in the pathway of pyrimidine biosynthesis, will be explored in this work. From a previous screening of 51 compounds against LmDHODH showed a benzothiazolinone with good inhibitory potential. The project aims evaluate the structure-activity relationship for this scaffold against LmDHODH by developing a small library of analogues.