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51.
Yun Chai Zhi-Long Wan Bo Wang Hui-Yuan Guo Ming-Liang Liu 《European journal of medicinal chemistry》2009,44(10):4063-4069
A series of novel 7-(4-alkoxyimino-3-amino-3-methylpiperidin-1-yl)fluoroquinolone derivatives were designed, synthesized and characterized by 1H NMR, MS and HRMS. These fluoroquinolones were evaluated for in vitro antibacterial activity against representative Gram-positive and Gram-negative strains. All of the title compounds have considerable activity against the twelve strains, and exhibit exceptional potency in inhibiting the growth of Staphylococcus aureus, Staphylococcus epidermidis and Klebsiella pneumoniae (minimum inhibitory concentration (MIC): 0.06–8 μg/mL). The most active compound 17 is 4-fold more potent than levofloxacin against S. aureus and S. epidermidis, 32-fold more potent than levofloxacin against Streptococcus pneumoniae, and 16-fold more potent than IMB against K. pneumoniae. 相似文献
52.
Yi‐Bin Zhang Lian‐Shun Feng Xue‐Fu You Qiang Guo Hui‐Yuan Guo Ming‐Liang Liu 《Archiv der Pharmazie》2010,343(3):143-151
A series of novel 7‐(3‐alkoxyimino‐4‐methyl‐4‐methylaminopiperidin‐1‐yl)fluoroquinolone derivatives were designed, synthesized, and characterized by 1H‐NMR, MS, and HRMS. These fluoroquinolones were evaluated for their in‐vitro antibacterial activity against representative Gram‐positive and Gram‐negative strains. Generally, all of the target compounds have considerable antibacterial activity against the tested forty strains, and exhibit exceptional potency in inhibiting the growth of methicillin‐sensitive Staphylococcus aureus (MSSA) and methicillin‐resistant S. aureus (MRSA) ATCC33591 (MICs: 0.06 to 2 μg/mL). In particular, compounds 14 , 19 , 28 , and 29 are fourfold more potent than ciprofloxacin against MSSA 08‐49. Compounds 23 , 26 , and 27 are twofold more potent than ciprofloxacin against MRSA ATCC33591 and MSSA ATCC29213. In addition, compound 14 exhibits excellent activity (MIC: 0.06 μg/mL) against Acinetobactes calcoaceticus, which is two‐ to 16‐fold more potent than the reference drugs gemifloxacin, levofloxacin, and ciprofloxacin. 相似文献
53.
Hiromi Ogino Miho Fujii Mariko Ono Kayoko Maezawa Seiji Hori Junko Kizu 《Journal of infection and chemotherapy》2009,15(3):168-173
Fluoroquinolones have been reported to affect cytokine production in vitro. We investigated the effects of fluoroquinolones
on lipopolysaccharide (LPS)-induced inflammatory cytokine production in vivo and in vitro. LPS was administered to mice treated
with ciprofloxacin, gatifloxacin, norfloxacin, and levofloxacin, and the serum levels of tumor necrosis factor α (TNF-α),
interleukin 1β (IL-1β), and interleukin 6 (IL-6) were measured. In addition, peritoneal macrophages collected from mice were
treated with the four fluoroquinolones for 1 h, followed by the addition of LPS, and the TNF-α, IL-1β, and IL-6 levels in
culture fluid were measured. In LPS-treated mice, ciprofloxacin, gatifloxacin, and norfloxacin (100 mg/kg) significantly reduced
the serum TNF-α level (6.8%–63.6% of control). Levofloxacin at 100 mg/kg did not affect the TNF-α level, whereas levofloxacin
at a lower dose (10 mg/kg) significantly increased the level. All four fluoroquinolones (100 mg/kg) investigated in this study
tended to decrease the serum IL-1β levels (65.5%–65.9% of control), but this was not a significant change. The serum IL-6
levels were increased in ciprofloxacin-administered mice, whereas the other fluoroquinolones did not affect the serum IL-6
levels. In mouse peritoneal macrophages, LPS induced TNF-α, IL-1β, and IL-6 production. Ciprofloxacin, gatifloxacin, and norfloxacin
(100 μg/ml) inhibited both TNF-α (12.1%–69.0% of control) and IL-1β production (22.1%–68.8% of control). Levofloxacin (100
μg/ml) inhibited IL-1β production (65.0% of control), but not TNF-α production. LPSstimulated IL-6 production was inhibited
only by norfloxacin (59.5 % of control). Our in vivo and in vitro results suggest that fluoroquinolones, especially ciprofloxacin,
gatifloxacin, and norfloxacin, which have a cyclopropyl group at the N1 position and/or a piperazinyl group at the C7 position,
modify inflammatory responses. 相似文献
54.
《Journal of chemotherapy (Florence, Italy)》2013,25(1):36-40
AbstractWe investigated the prevalence of plasmid-mediated quinolone resistance genes in 756 clinical isolates of Enterobacteriaceae originating from Microbiology Diagnostic Laboratories of North-East Italy. Five point zero two percent of isolates carried a qnr determinant while the aac(6')-Ib-cr determinant was detected in 9·25% of isolates. We also investigated the association between the plasmid-mediated quinolone resistance and the beta-lactamase genes, and characterized the plasmids carrying these determinants of resistance. 相似文献
55.
Hiromi Ogino Kaori Yamada Mizuki Yuhara Saori Tsuchida Kayoko Maezawa Junko Kizu Seiji Hori 《Journal of infection and chemotherapy》2009,15(2):113-117
We studied the effect of fluoroquinolones (FQs) on carrageenan-induced edema in the rat footpad. Ciprofloxacin, gatifloxacin,
sparfloxacin, norfloxacin, and enoxacin (s.c., 100 mg/kg), which have piperazinyl and/or cyclopropyl groups, inhibited carrageenan-induced
edema, whereas levofloxacin, tosufloxacin, and pazufloxacin did not. The reduction of edema by ciprofloxacin, sparfloxacin,
and enoxacin was abolished by pretreatment with mifepristone, an antagonist of the glucocorticoid receptor. These results
suggest that FQs with piperazinyl and/or cyclopropyl groups can modify biological responses through enhancing the glucocorticoid-glucocorticoid
receptor system. 相似文献
56.
Dewan Sakhawat Billal Muneki Hotomi Steve S. Yan Daniel P. Fedorko Jun Shimada Keiji Fujihara Noboru Yamanaka 《Diagnostic microbiology and infectious disease》2009
In the past 2 to 3 decades, erythromycin resistance in Streptococcus pyogenes has been decreasing, whereas fluoroquinolone resistance (or reduction in its susceptibility) has been reported often. Although a shift of M-type prevalence and decreased pressure from macrolides have been suggested for the decrease in erythromycin resistance, we hypothesized that this might also be a result of increased antimicrobial pressure from fluoroquinolone use. Levofloxacin resistance for 4 erythromycin-resistant parent strains was induced in vitro. Their mutants became highly resistant to the fluoroquinolones but lost their erythromycin resistance trait. Erythromycin resistance was fully restored by transconjugation with respective parent strains with either mefA- or ermTR-mediated mechanisms. 相似文献
57.
Design, synthesis and activity against Toxoplasma gondii, Plasmodium spp., and Mycobacterium tuberculosis of new 6-fluoroquinolones 总被引:2,自引:0,他引:2
Anquetin G Greiner J Mahmoudi N Santillana-Hayat M Gozalbes R Farhati K Derouin F Aubry A Cambau E Vierling P 《European journal of medicinal chemistry》2006,41(12):1478-1493
This paper reports on the rational design of a series of new 6-fluoroquinolones by QSAR analysis against Toxoplasma (T.) gondii, their synthesis, their biological evaluation against T. gondii and Plasmodium (P.) spp., and their effect on Mycobacterium (M.) tuberculosis DNA gyrase and growth inhibition. Of the 12 computer-designed 8-ethyl(or methoxy)- and 5-ethyl-8-methoxy-6-fluoroquinolones predicted to be active against T. gondii, we succeeded in the synthesis of four 6-fluoro-8-methoxy-quinolones. The four 6-fluoro-8-methoxy-quinolones are active on T. gondii but only one is as active as predicted. One of these four compounds appears to be an antiparasitical drug of great potential with inhibitory activities comparable to or higher than that of trovafloxacin, gatifloxacin, and moxifloxacin. They also inhibit DNA supercoiling by M. tuberculosis gyrase with an efficiency comparable to that of the most active quinolones but are poor inhibitors of M. tuberculosis growth. 相似文献
58.
Berger P Pascal L Sartor C Delorme J Monge P Ragon CP Charbit M Sambuc R Drancourt M 《European journal of epidemiology》2004,19(5):453-460
Mathematical models currently used to study the relationship between the prevalence of the resistance to an antibiotic and the amount of drug may not be adequate because they do not integrate temporal and area analyses simultaneously. Furthermore, the forms of such relationship are unknown. We applied the Generalized Additive Model (GAM) to study fluoroquinolone use and the incidence of fluoroquinolone-resistance in Staphylococcus aureus in our institution over a 3-year period. Overall institution and individual hospital unitrestricted analyses were performed. Relative risk (RR) observed for increasing fluoroquinolone use with a 4-month lag from the 25th percentile to the 75th percentile was 1.27 (95% CI: 1.13-1.42). In the surgery units, RR was 1.23 (95% CI: 1.01-1.50) for fluoroquinolone use with a 2-months lag. GAM enabled us to observe for the first time a significant temporal relationship between fluoroquinolone use and the incidence of fluoroquinolone-resistant nosocomial S. aureus isolates. 相似文献
59.
妥舒沙星前药的合成及其体内抗菌活性 总被引:2,自引:0,他引:2
分别以N-叔丁氧羰基-L-亮氨酸(L-缬氨酸)和妥舒沙星盐酸盐为原料,经缩合后在盐酸中水解得到含有L-亮氨酰基或L-缬氨酰基的2种妥舒沙星前药的盐酸盐(1a,b)。测定了它们及对照药对小鼠腹腔感染不同细菌的体内保护疗效,结果表明,1b对肺炎链球菌9798和金葡球菌15的体内活性均弱于对甲苯磺酸妥舒沙星(TSFX·TosOH);1a对肺炎链球菌9798、金葡球菌15和金葡球菌01193的体内活性均强于TSFX·TosOH。1a具有潜在的开发价值,值得进一步深入评价。 相似文献
60.
6种氟喹诺酮类药物的体外抗解脲脲原体作用 总被引:4,自引:1,他引:4
目的;研究检测解脲脲原体(Uu)临床株对氟喹诺酮类药物的敏感性,为临床治疗提供参考依据。方法:应用微量肉汤稀释法检测了88株Uu对6种氟喹诺酮类药物的敏感性。结果:在6种药物中司帕沙星和加替沙星抗Uu活性最强,MIC50分别为0.25μg/ml和0.5μg/ml,MIC90均为4μg/ml。其次为左氧氟沙星和氧氟沙星,MIC50分别为1μg/ml和2μg/ml,MIC90分别为4μg/ml和8μg/ml。诺氟沙星和环丙沙星的抗Uu活性最差。结论:氟喹诺酮类抗菌药新品种司帕沙星,左氧氟沙星和加替沙量的抗Uu活性较老一代药物更强;Uu对老一代氟喹诺酮类药物存在不同程度的耐药。 相似文献