SAR and Anti-Mycobacterial Activity of Quinolones and Triazoloquinolones: An Update
Maria A. Pirisi,
Fluoroquinolones (FQ) are an important family of synthetic antimicrobial agents being clinically used over the
past thirty years. Currently some FQ are under investigation for the treatment of multidrug-resistant tuberculosis (MDRTB),
defined as resistance to at least isoniazid and rifampicin, and are under investigation as first-line drugs. Their main
biological target in Mycobacterium tuberculosis is the DNA gyrase, a topoisomerase II encoded by gyrA and gyrB that is
essential to maintain the DNA supercoil. It has been demonstrated that mutations in short regions of DNA gyrase are associated
with quinolone resistance or hypersusceptibility and take place in several MDR clinical isolates of M. tuberculosis.
In this article we update§ our previous review (Carta et al. Anti-infective agents, 2008, 7, 134-147) about the anti mycobacterial
properties, mode of action and structure activity relationship (SAR) studies of the known quinolone derivatives. Furthermore,
we update the synthesis and activity of 3,9-disubstituted-6-oxo-6,9-dihydro-3H-[1,2,3]-triazolo[4,5-h,g]quinolonecarboxylic
acids and their esters as a new class of potent and selective anti-mycobacterial agents, coupled with absence of
cytotoxicity. Furthermore, particularly interesting is their activity against MDR M. tuberculosis.
Keywords: Anti-mycobacterial activity, DNA gyrase inhibitors, MDR-TB, quinolones, SAR analysis, triazoloquinolones antitubercular
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