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.