Rational design, synthesis and anti-tubercular evaluation of novel 1H-1,2,3-triazole-linked gatifloxacin and isatin hybrids
Hybridization,which is on the basis of the combination of two or more different pharmacophore moieties of different bioactive substances resulting into a new molecule,has been emerged as one of the most useful structural modification tool to design agents with better pharmacophoric properties.A new class of 1-cyclopropyl-7-(4-((1-(2-(2,3-dioxoindolin-1-yl)-2-oxoethyl)-1 H-1,2,3-triazol-4-yl)methyl)-3-methylpiper azin-1-yl)-6-fluoro-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid hybrids designed by hybridizing three anti-tuberculosis bioactive substances/pharmacophoric units gatifloxacin (GTFX),I-A09 and isatin in a single molecular architecture,were synthesized and evaluated for their in vitro anti-mycobacterial activity against M.smegmatis and M.tuberculosis (MTB) H37Rv.The preliminary results showed that all hybrids (MIC: 6.25-100 μg/mL) exhibited considerable activity against M.smegmatis,but less active than the parent GTFX (MIC: 3.12 μg/mL) and the reference INH (MIC: 0.78 μg/mL).Against MTB H37Rv,all hybrids displayed excellent inhibitory activity with MICs ranging from 0.39 to 12.5 μg/mL,particularly,5d (MIC: 0.39μg/mL) with low cytotoxicity (CC50:151.2 μg/mL) was 2-fold more potent than GTFX (MIC: 0.78 μg/mL) and comparable to RIF (MIC: 0.39/zg/mL),warrant further investigations.
gatifloxacin isatin triazole conjugates anti-tuberculosis activity structure-active relationship
Zhi Xu Yuan-Bo Fu Yuan-Qiang Hu
Wuhan University of Science and Technology;Wuhan oxiran special chemicals co,.LTD Wuhan oxiran special chemicals co,.LTD College of Chemistry and Materials Science, Hubei Engineering University, Hubei, P R China
国内会议
江苏扬州
英文
495-504
2017-04-16（万方平台首次上网日期，不代表论文的发表时间）