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Candidate vaginal microbicides with activity against Chlamydia trachomatis and Neisseria gonorrhoeae
Umeå University, Faculty of Science and Technology, Department of Chemistry.
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2010 (English)In: International Journal of Antimicrobial Agents, ISSN 0924-8579, E-ISSN 1872-7913, Vol. 36, no 2, 145-150 p.Article in journal (Refereed) Published
Abstract [en]

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 microM towards C. trachomatis L2. Three INPs had a MIC <12.5 microM against N. gonorrhoeae. Inhibition 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.

Place, publisher, year, edition, pages
2010. Vol. 36, no 2, 145-150 p.
Keyword [en]
vaginal microbicide, sexually transmitted infections, chlamydia trachomatis, LGV, Neisseria gonorrhoeae
URN: urn:nbn:se:umu:diva-35280DOI: 10.1016/j.ijantimicag.2010.03.018ISI: 000278870300010PubMedID: 20605703OAI: diva2:342872
Available from: 2010-08-11 Created: 2010-08-11 Last updated: 2010-09-23Bibliographically approved

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Elofsson, Mikael
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