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101.
利用3D-QSAR中的CoMFA方法研究了1-环丙基-5-取代-7-(4-甲基哌嗪基)-6,8-二氟-1,4-二氢-4-氧-3-喹啉羧酸定量构效关系。研究表明,从PLS分析的rcv,r值看,模型有效强的预测能力;从立体与静电作用分数比可看出,5位取代基对活性的影响立体效应起主要作用,但静电效应亦十分重要。依据CoMFA系数图设计了一些新化合物,预测结果表明,以5位氨基对抑制革兰氏阳性、阴性菌的活性为最高,与近几年实验研究的结果一致. 相似文献
102.
以 ( 4R) 羟基 L 脯氨酸为原料 ,经十三步反应得 ( 1S ,5R) 2 苄基 2 ,6 二氮杂二环 ( 3.2 .1)辛烷二氢溴酸盐 ,以此化合物作为 7位侧链 ,合成了四个喹诺酮类化合物 ,并测定了它们对 10株革兰氏阳性菌和 6株革兰氏阴性菌的MIC值 ,结果表明 ,它们的体外抗菌作用均低于对照药加替沙星和环丙沙星。本文共合成了 2 0个化合物 ,除 2、3、4外 ,其余均为文献未见报道的新化合物 ,其结构经NMR和MS所确证。 相似文献
103.
洛美沙星的药效学研究 总被引:2,自引:0,他引:2
洛美沙星为一新型氟喹诺酮类药物,其抗菌谱广,抗菌作用强,本文报道其体内外抗菌作用的研究结果。洛美沙星对革兰氏阴性菌具强大的抗菌作用,其MIC_(90)大都≤2mg/L,对大肠杆菌、流感杆菌和淋球菌的抗菌作用尤强,对肺炎球菌和其他链球菌的抗菌作用较弱。对大部分耐庆大霉素和哌拉西林的革兰氏阳性杆菌仍具良好抗菌活性。洛美沙星的抗菌作用略逊于环丙沙星,与氧氟沙星相似,稍优于诺氟沙星。洛美沙星对小鼠实验性细菌感染,尤其是革兰氏阳性杆菌感染具有明显保护作用,其口服用药后的体内抗菌作用明显优于诺氟沙星。 相似文献
104.
Eighteen 7-substituted-1-ethyl (2-fluoroethyl)-6, 8-difluoro-1, 4-dihydro-4-oxoquinolone-3-carboxylic acid were designed and synthesized. The results of preliminary antibacterial test showed that most of the compounds exhibited definite activities in test against pathogenic bacteria. Especially, compound 17 and 18 showed better activities and surpassed fleroxacin when compared in vitro. 相似文献
105.
Development of a rapid assay for screening point mutations associated with quinolone resistance in the Pseudomonas aeruginosa parC gene 总被引:1,自引:0,他引:1
Takashi Deguchi Masayoshi Yamaha Masahiro Nakano Mitsuru Yasuda Yoshinori Nishino Satoshi Ishihara Yukimichi Kawada 《Journal of infection and chemotherapy》2000,6(1):26-29
To detect quinolone resistance-associated mutations within the Ser-80 and Glu-84 codons of the Pseudomonas aeruginosa parC gene, we developed a rapid and simple assay based on polymerase chain reaction (PCR) amplification of the region of the parC gene containing the mutation sites and digestion of the PCR products with a restriction enzyme. The mutations generating
alterations at Ser-80 and Glu-84 were detected as restriction fragment length polymorphisms of the PCR products digested with
HinfI. Among 22 clinical isolates tested by this assay, mutations at the Ser-80 and Glu-84 codons were detected in all 10 isolates
in which the presence of the mutations had been confirmed previously by DNA sequencing. This rapid and simple assay could
be a useful screening device for genetic alterations associated with resistance to quinolones in the P. aeruginosa parC gene.
Received: June 10, 1999 / Accepted: October 8, 1999 相似文献
106.
T. Hara H. Takemura K. Kanemitsu H. Yamamoto J. Shimada 《Journal of infection and chemotherapy》2000,6(3):162-167
The present study was designed to compare the uptake of grepafloxacin by a human monocytic cell line, THP-1, with that of
ciprofloxacin. THP-1 cells were incubated with 20 μg/ml of either drug, and the entry of the drugs into the cells was determined
using a velocity gradient centrifugation technique and HPLC assay. Antibiotic uptake by the cells was expressed as the ratio
of the intracellular to the extracellular drug concentration (IC/EC). Grepafloxacin entered THP-1 cells readily within 5 min,
and at steady-state (37°C; 60 min), the IC/EC ratio of grepafloxacin (11.9 ± 1.7; n = 13) was about 2.4-fold higher than that of ciprofloxacin (5.0 ± 1.3; n = 13). The ratios decreased at low incubation temperature (4°C), in paraformaldehyde-treated dead cells, and at low extracellular
pH (pH 6.0), but were not influenced by high extracellular pH (pH, 9.0). Characterization of fluoroquinolone uptake suggests
that these drugs penetrate the THP-1 membrane by passive diffusion, and also, in part, via an active transport system. We
also examined the uptake of the two fluoroquinolones in phorbol 12 myristate 13-acetate (PMA)-stimulated adherent THP-1 cells
(THP-1 macrophages). The IC/EC ratios for both fluoroquinolones in the THP-1 macrophages were significantly higher than those
in the THP-1 monocytes. Further the uptake of three other fluoroquinolones, levofloxacin, tosufloxacin, and sparfloxacin,
by THP-1 monocytes was examined in comparative studies. The IC/EC ratio of grepafloxacin was comparable to that of sparfloxacin
and significantly higher than that of the other fluoroquinolones. Our results indicate that grepafloxacin exhibits better
intracellular accumulation than ciprofloxacin and other fluoroquinolones in human monocytic and macrophage-like cells.
Received: June 1, 2000 / Accepted: August 1, 2000 相似文献
107.
《Current medical research and opinion》2013,29(1):93-94
ABSTRACTA prospective, double-masked, randomized, parallel-group study (n = 25) was conducted to examine the ocular penetration of moxifloxacin 0.5% ophthalmic solution and gatifloxacin 0.3% solution into the aqueous humor following topical administration prior to routine cataract surgery. One drop of antibiotic was instilled every 10?min for four doses beginning 1?h prior to surgery. Preliminary results showed aqueous humor concentrations for moxifloxacin that were significantly greater (?p < 0.01) than those for gatifloxacin. 相似文献
108.
109.
In the present study, we assessed the ecotoxicological effects of selected human and veterinary antibiotics to D. magna. Ecological risk assessment was done by calculating the risk quotients (RQs) of the antibiotics to the species. Results showed that enrofloxacin, a veterinary fluoroquinolone antibiotic, was the most toxic against D. magna with a 48 h EC50 value of 28.59 mg/l. The binary mixture of fluoroquinolones was also more toxic to the species than binary mixtures of macrolides. Fecundity in organisms in negative control was higher than fecundity in organisms exposed to environmentally relevant concentrations of the four antibiotics. Enrofloxacin also has a moderate risk to the species with RQ values of 0.199 and 0.416 in surface waters and wastewaters, respectively. Antibiotics pose a greater ecological risk when present in mixtures in the aquatic environment. Environmental standards for pharmaceuticals should incorporate mixture toxicity data to ensure accurate protection of non-target organisms in polluted environments. 相似文献
110.
Soil and sludge are major reservoirs of organic compounds such as fluoroquinolones (FQs) which are broad-spectrum antibacterial agents. Hence, we monitored three major FQs, namely, ciprofloxacin (CIP), norfloxacin (NOR), and ofloxacin (OFL), in surface soil from two major dumpsites and dry and wet sludge from sewage treatment plants in Chennai city. The mean concentration of FQs in soil and sludge samples were 20 μg/g and 26 μg/g, respectively. Nearly 50% of the total FQs in dumpsite soil was contributed by CIP followed by NOR (32%) and OFL (13%). Similarly, CIP was the major contributor in sludge samples followed by NOR and OFL. The concentration of FQs was two folds higher in wet sludge than dry sludge most likely indicating that water solubility of these compounds might play an important role for elevated level of FQs in wet sludge. Solid waste from pharmaceutical industries, households, and sludge from wastewater treatment plants were expected to be the major source of FQs in dumpsite soil. Predicted risk assessment using soil to water migration concentrations via surface run off indicated high risk to aquatic organisms. However, risk quotient (RQ) was found less to earthworm in most of the soil samples. The findings from this study might help in future policies on disposal of household antibiotics in the solid waste stream. 相似文献