Candidate vaginal microbicides with activity against Chlamydia trachomatis and Neisseriagonorrhoeae.
Candidate vaginal microbicides with activity against Chlamydia trachomatis and Neisseriagonorrhoeae.
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DOI：
10.1016/j.ijantimicag.2010.03.018
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发表时间：
2010-08
影响因子：
10.8
通讯作者：
Peterson EM
中科院分区：
文献类型：
--
作者：
Chu H;Slepenkin A;Elofsson M;Keyser P;de la Maza LM;Peterson EM
已提出使用对引起性传播感染的有机体具有活性的阴道杀微生物剂作为减少传播的一项战略。属于水杨醛酰肼类（INPs）的沙眼衣原体血清型D的小分子抑制剂已被证明通过涉及铁限制的机制起作用。在这项工作的基础上，对10种INPs进行了抗性病性淋巴肉芽肿C.沙眼血清型L2、淋病奈瑟氏菌和产生过氧化氢的卷曲乳杆菌和詹氏乳杆菌。7种INPs对C的最小抑菌浓度（MIC）和最小杀菌浓度<50 µM。沙眼衣原体L2。三种INPs对N的MIC <12.5 µM。淋病铁，全转铁蛋白和全乳铁蛋白，但不是由这些化合物的铁贫形式逆转的抑制。这些化合物对乳酸杆菌没有杀菌活性。INPs对HeLa 229细胞无细胞毒性。当在衣原体阴道感染的小鼠模型中测试INP 0341时，脱落衣原体的小鼠数量显著减少。感染后4天内沙眼衣原体感染率显著高于感染前（P < 0.01）。总之，选择的INPs是有希望的阴道杀微生物剂候选物，因为它们在体外抑制两种常见的性传播生物的生长，在小鼠模型中对C.沙眼，没有细胞毒性并且不抑制组成正常阴道植物群的生物体。
Vaginal microbicides with activity towards organisms that cause sexually transmitted infections have been proposed as a strategy to reduce transmission. Small-molecule inhibitors of Chlamydia trachomatis serovar D belonging to the class of salicylidene acylhydrazides (INPs) have been shown to work through a mechanism that involves iron restriction. Expanding on this work, ten INPs were tested against a lymphogranuloma venereum strain of C. trachomatis serovar L2, Neisseria gonorrhoeae, and hydrogen peroxide-producing Lactobacillus crispatus and Lactobacillus jensenii. Seven INPs had minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations of <50 µM towards C. trachomatis L2. Three INPs had an MIC <12.5 µM against N. gonorrhoeae. Inhibition by was reversed by iron, holo-transferrin and holo-lactoferrin but not by the iron-poor forms of these compounds. The compounds exhibited no bactericidal activity toward Lactobacillus. The INPs were not cytotoxic to HeLa 229 cells. When INP 0341 was tested in a mouse model of a Chlamydia vaginal infection there was a significant reduction in the number of mice shedding C. trachomatis up to 4 days after infection (P < 0.01). In summary, select INPs are promising vaginal microbicide candidates as they inhibit the growth of two common sexually transmitted organisms in vitro, are active in a mouse model against C. trachomatis, are not cytotoxic and do not inhibit organisms that compose the normal vaginal flora.
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影响因子：
3.1
作者：
Nordfelth, R;Kauppi, AM;Elofsson, M
通讯作者：
Elofsson, M
影响因子：
3.6
作者：
Nieuwenhuis, RF;Ossewaarde, JM;Neumann, HAM
通讯作者：
Neumann, HAM
影响因子：
3.8
作者：
LAGA, M;MANOKA, A;PIOT, P
通讯作者：
PIOT, P
影响因子：
11.8
作者：
Nieuwenhuis, RF;Ossewaarde, JM;van der Meijden, WI
通讯作者：
van der Meijden, WI
影响因子：
6.4
作者：
Kapiga, Saidi H.;Sam, Noel E.;Essex, Max
通讯作者：
Essex, Max