SAR and Anti-Mycobacterial Activity of Quinolones and Triazoloquinolones: An Update

E-ISSN： 2211-3533|11|1|76-90

ISSN： 2211-3525

Source： Anti-Infective Agents, Vol.11, Iss.1, 2012-11, pp. : 76-90

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Abstract

Fluoroquinolones (FQ) are an important family of synthetic antimicrobial agents being clinically used over thepast 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 mainbiological target in Mycobacterium tuberculosis is the DNA gyrase, a topoisomerase II encoded by gyrA and gyrB that isessential to maintain the DNA supercoil. It has been demonstrated that mutations in short regions of DNA gyrase are associatedwith quinolone resistance or hypersusceptibility and take place in several MDR clinical isolates of M. tuberculosis.In this article we update^#167; our previous review (Carta et al. Anti-infective agents, 2008, 7, 134-147) about the anti mycobacterialproperties, 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]quinolonecarboxylicacids and their esters as a new class of potent and selective anti-mycobacterial agents, coupled with absence ofcytotoxicity. Furthermore, particularly interesting is their activity against MDR M. tuberculosis.