Pre-clinical pharmacokinetics and anti-chlamydial activity of salicylidene acylhydrazide inhibitors of bacterial type III secretion.
Pre-clinical pharmacokinetics and anti-chlamydial activity of salicylidene acylhydrazide inhibitors of bacterial type III secretion.
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临床前的药代动力学和抗细胞活性的抗氯二酰氢氮酰抑制剂III型分泌。
DOI：
10.1038/ja.2012.43
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发表时间：
2012-08
期刊：
影响因子：
--
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中科院分区：
文献类型：
--
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水杨酰肼是一类能抑制致病革兰氏阴性菌分泌细菌III型(T3s)的化合物。这类化合物还抑制衣原体的生长和复制，衣原体是一种严格的细胞内细菌，拥有T3S系统。在这项研究中，我们筛选了一个包含58种水杨醛酰肼的文库来鉴定衣原体生长的抑制物。对抑制沙眼衣原体和肺炎衣原体生长的化合物进行了细胞毒性试验，并选择了7个化合物进行了初步的小鼠药代动力学分析。对两个化合物ME0177和ME0192进行了个体药代动力学分析。化合物ME0177具有较高的峰浓度(Cmax)和曲线下面积，可用于全身治疗衣原体感染。另一种化合物ME0192的药代动力学特性较差，但体外抗衣原体活性最高，因此在小鼠阴道感染模型上进行了局部治疗。ME0192经阴道给药可显著降低沙眼衣原体的感染负担和感染小鼠的数量。
Salicylidene acylhydrazides belong to a class of compounds shown to inhibit bacterial type III secretion (T3S) in pathogenic Gram-negative bacteria. This class of compounds also inhibits growth and replication of Chlamydiae, strict intracellular bacteria that possess a T3S system. In this study a library of 58 salicylidene acylhydrazides was screened to identify inhibitors of Chlamydia growth. Compounds inhibiting growth of both Chlamydia trachomatis and Chlamydophila pneumoniae were tested for cell toxicity and seven compounds were selected for preliminary pharmacokinetic analysis in mice using cassette dosing. Two compounds, ME0177 and ME0192, were further investigated by individual pharmacokinetic analysis. Compound ME0177 had a relatively high peak plasma concentration (Cmax) and area under curve and therefore may be considered for systemic treatment of Chlamydia infections. The other compound, ME0192, had poor pharmacokinetic properties but the highest anti-chlamydial activity in vitro and therefore was tested for topical treatment in a mouse vaginal infection model. ME0192 administered vaginally significantly reduced the infectious burden of C. trachomatis and the number of infected mice.
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影响因子：
3.6
作者：
Wolf, K.;Betts, H. J.;Fields, K. A.
通讯作者：
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DOI：
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发表时间：
2010-08
影响因子：
10.8
作者：
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通讯作者：
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影响因子：
3.1
作者：
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通讯作者：
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影响因子：
3.5
作者：
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通讯作者：
Bergstrom, Sven
DOI：
10.1073/pnas.0606412103
发表时间：
2006-09-26
影响因子：
11.1
作者：
Muschiol, Sandra;Bailey, Leslie;Henriques-Normark, Birgitta
通讯作者：
Henriques-Normark, Birgitta