[1,2,3]Triazolo[4,5-h]quinolones. A new class of potent antitubercular agents against multidrug resistant Mycobacterium tuberculosis strains.
In this preliminary study we report the activity of 3-methyl-9-substituted-6-oxo-6,9-dihydro-3H-[1,2,3]-triazolo[4,5-h]quinolone-carboxylic acids and their esters as a new class of antiinfective agents against MDR Mycobacterium tuberculosis. In antitubercular screening against H37Rv and 11 clinically isolated strains of M. tuberculosis several derivatives (1o,3a,c,i,j,p) showed MIC(90) in the range 0.5-3.2 microg/mL. 3c showed no cytotoxicity and proved to be the most potent derivative exhibiting MIC(90)=0.5 microg/mL against all M. tuberculosis strains and infected human macrophages (J774-A1) tested.
Carta
Antonio
A
Dipartimento Farmaco Chimico Tossicologico, Università degli Studi di Sassari, Via Muroni 23/a, 07100, Sassari, Italy. acarta@uniss.it
Palomba
Michele
M
Paglietti
Giuseppe
G
Molicotti
Paola
P
Paglietti
Bianca
B
Cannas
Sara
S
Zanetti
Stefania
S
D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D024881:Drug Resistance, Bacterial; D018432:Drug Resistance, Multiple; D006801:Humans; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests; D008956:Models, Chemical; D009169:Mycobacterium tuberculosis / Q000378:metabolism*; D015363:Quinolones / Q000737:chemistry*; D014230:Triazoles / Q000737:chemistry*; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy*
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D015363:Quinolones; D014230:Triazoles