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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Target Sites for the Design of Anti-trypanosomatid Drugs Based on the Structure of Dihydroorotate Dehydrogenase

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Author(s):
Pinheiro, Matheus Pinto [1] ; Emery, Flavio da Silva [2] ; Cristina Nonato, M. [1]
Total Authors: 3
Affiliation:
[1] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Fis & Quim, Lab Cristalog Prot, BR-14040903 Ribeirao Preto, SP - Brazil
[2] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Ciencias Farmaceut, BR-14040903 Ribeirao Preto, SP - Brazil
Total Affiliations: 2
Document type: Journal article
Source: CURRENT PHARMACEUTICAL DESIGN; v. 19, n. 14, p. 2615-2627, APR 2013.
Web of Science Citations: 18
Abstract

Trypanosomatids consist of a large group of flagellated parasitic protozoa, including parasites from the genera Leishmania and Trypanosoma, responsible for causing infections in millions of humans worldwide and for which currently no appropriate therapy is available. The significance of pyrimidines in cellular metabolism makes their de novo and salvage pathways ideal druggable targets for pharmacological intervention and open an opportunity for pharmaceutical innovation. In the current review, we discuss the merits in targeting the enzyme dihydroorotate dehydrogenase (DHODH), a flavin-dependent enzyme that catalyzes the fourth and only redox step in pyrimidine de novo biosynthesis, as a strategy for the development of efficient therapeutic strategies for trypanosomatid-related diseases. We also describe the advances and perspectives from the structural biology point of view in order to unravel the structure-function relationship of trypanosomatid DHODHs, and to identify and validate target sites for drug development. (AU)

FAPESP's process: 09/14184-0 - Antiinfective compounds: bringing together medicinal chemistry and organic synthesis in search of lead antiparasitic compounds
Grantee:Flavio da Silva Emery
Support Opportunities: Regular Research Grants
FAPESP's process: 07/08703-0 - Design of inhibitors for dihydroorotate dehydrogenase from Trypanosoma cruzi and Leishmania major
Grantee:Matheus Pinto Pinheiro
Support Opportunities: Scholarships in Brazil - Doctorate