Folate biosynthesis pathway: mechanisms and insights into drug design for infectious diseases

Author:

Bertacine Dias Marcio V123,Santos Jademilson C1,Libreros-Zúñiga Gerardo A134,Ribeiro João A12,Chavez-Pacheco Sair M1

Affiliation:

1. Universidade de São Paulo, Instituto de Ciências Biomédicas, Departamento de Microbiologia, Avenida Professor Lineu Prestes, 1374, Butantã, 05508000, São Paulo, SP, Brasil

2. Universidade Estadual de Campinas, Programa de Pós-Graduação em Biociências e Tecnologia de Produtos Bioativos, Instituto de Biologia, CPG/IB/UNICAMP, Rua Monteiro Lobato, 255, Cidade Universitária, CEP 13083–862, Campinas/SP, Brazil

3. Universidade Estadual Paulista, Instituto de Biociências, Letras e Ciências Exatas – IBILCE, Rua Cristóvão Colombo, 2265, São José do Rio Preto, São Paulo, 15054–000, Brasil

4. Universidad del Valle, Facultad de Salud, Escuela de Ciencias Básicas, Departamento de Microbiología, Calle 4B # 36–00, Cali, Valle, Colombia

Abstract

Folate pathway is a key target for the development of new drugs against infectious diseases since the discovery of sulfa drugs and trimethoprim. The knowledge about this pathway has increased in the last years and the catalytic mechanism and structures of all enzymes of the pathway are fairly understood. In addition, differences among enzymes from prokaryotes and eukaryotes could be used for the design of specific inhibitors. In this review, we show a panorama of progress that has been achieved within the folate pathway obtained in the last years. We explored the structure and mechanism of enzymes, several genetic features, strategies, and approaches used in the design of new inhibitors that have been used as targets in pathogen chemotherapy.

Publisher

Future Science Ltd

Subject

Drug Discovery,Pharmacology,Molecular Medicine

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