title: Synthesis and evaluation of a pyrazinoic acid prodrug in Mycobacterium tuberculosis.
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.
authors.affiliation: Institute of Environmental, Chemical and Pharmaceutical Sciences, Federal University of São Paulo (UNIFESP), Brazil.
authors.forename: João Paulo-Dos Santos
authors.initials: JP
authors.lastname: Fernandes
authors.affiliation: Department of Biological Sciences, Faculty of Pharmaceutical Sciences, State University of São Paulo (UNESP), Brazil.
authors.forename: Fernando Rogerio
authors.initials: FR
authors.lastname: Pavan
authors.affiliation: Department of Biological Sciences, Faculty of Pharmaceutical Sciences, State University of São Paulo (UNESP), Brazil.
authors.forename: Clarice Queico Fujimura
authors.initials: CQ
authors.lastname: Leite
authors.affiliation: Department of Pharmacy, Faculty of Pharmaceutical Sciences, University of São Paulo (USP), Brazil.
authors.forename: Veni Maria Andres
authors.initials: VM
authors.lastname: Felli
keywords: Antimycobacterial agent; Ester synthesis; Prodrug; Pyrazinoic acid; Tuberculostatic