Corrêa Michelle Fidelis, Fernandes João Paulo-dos Santos
Departamento de Ciências Exatas e da Terra, Universidade Federal de São Paulo, Rua São Nicolau 210, 2º andar, 09913-030 Centro, Diadema SP, Brazil.
Curr Protein Pept Sci. 2016;17(3):213-9. doi: 10.2174/1389203716666151002114839.
Tuberculosis (TB) is an infectious diseases responsible for thousands of deaths worldwide. Due to the use of antimycobacterial drugs, TB prevalence seemed to be controlled, but with the appearance of resistant tuberculosis cases, the concern about the disease had become significant again, as well as the need for new alternatives to TB treatment. Since pyrazinamide (PZA) is part of the firstline agents in TB treatment, several derivatives of this drug were described, besides pyrazinoic acid (POA) derivatives, the active form of PZA. POA has been used mainly to design prodrugs to be activated by mycobacterial esterases, while PZA derivatives should be activated specifically by the nicotinamidase/ pyrazinamidase (PZAse), or other PZAse-independent pathways. The intention of this paper is to discuss the state of art of PZA and POA derivatives and their activity against Mycobacterium tuberculosis and other mycobacteria, besides the therapeutic potential. Focus was given in prodrugs and derivatives directed to mycobacterial enzymes involved in its activation or mechanism of action.
结核病（TB）是一种在全球导致数千人死亡的传染病。由于抗分枝杆菌药物的使用，结核病的流行似乎得到了控制，但随着耐药结核病例的出现，对该疾病的担忧以及对结核病治疗新替代方案的需求再次变得显著。由于吡嗪酰胺（PZA）是结核病治疗一线药物的一部分，除了吡嗪酰胺的活性形式吡嗪酸（POA）衍生物外，还描述了该药物的几种衍生物。POA主要用于设计由分枝杆菌酯酶激活的前药，而PZA衍生物应通过烟酰胺酶/吡嗪酰胺酶（PZAse）或其他不依赖PZAse的途径特异性激活。本文旨在讨论PZA和POA衍生物的现状及其对结核分枝杆菌和其他分枝杆菌的活性，以及其治疗潜力。重点关注针对参与其激活或作用机制的分枝杆菌酶的前药和衍生物。
