Title of article :
Synthesis and evaluation of a pyrazinoic acid prodrug in Mycobacterium tuberculosis
Author/Authors :
Fernandes, Joa˜o Paulo-dos Santos Federal University of Sa˜o Paulo (UNIFESP) - Institute of Environmental, Chemical and Pharmaceutical Sciences, Brazil , Pavan, Fernando Rogerio State University of Sa˜o Paulo (UNESP) - Faculty of Pharmaceutical Sciences - Department of Biological Sciences, Brazil , Leite, Clarice Queico Fujimura State University of Sa˜o Paulo (UNESP) - Faculty of Pharmaceutical Sciences - Department of Biological Sciences, Brazil , Felli, Veni Maria Andres University of Sa˜o Paulo (USP) - Faculty of Pharmaceutical Sciences - Department of Pharmacy, Brazil
Abstract :
Tuberculosis (TB) is a disease caused mainly by infection of Mycobacterium tuberculosis affecting more than ten million people around the world. Despite TB can be treated, the rise of MDR-TB and XDR-TB cases put the disease in a worrying status. As pyrazinamide-resistant strains exhibit low or none pyrazinamidase activity, it is proposed that the active form of pyrazinamide (PZA) is pyrazinoic acid (POA), although this acid has poor penetration in mycobacteria. In this work, we present a convenient one-pot synthesis of 2-chloroethyl pyrazinoate, and its activity in M. tuberculosis H37Rv (ATCC27294) in MIC assay using the MABA technique. The obtained MIC of the compound was 3.96 g/mL, and discussion about the activity profile of some previously evaluated pyrazinoates is also performed.
Keywords :
Antimycobacterial agent , Ester synthesis , Prodrug , Pyrazinoic acid , Tuberculostatic
Journal title :
Saudi Pharmaceutical Journal(SPJ)
Journal title :
Saudi Pharmaceutical Journal(SPJ)
