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Pre-clinical pharmacokinetics and anti-chlamydial activity of salicylidene acylhydrazide inhibitors of bacterial type III secretion
Umeå University, Faculty of Science and Technology, Department of Chemistry.
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2012 (English)In: The Journal of antibiotics, ISSN 0021-8820, Vol. 65, 397-404 p.Article in journal (Refereed) Published
Abstract [en]

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 (C(max)) 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.Journal of Antibiotics advance online publication, 6 June 2012; doi:10.1038/ja.2012.43.

Place, publisher, year, edition, pages
2012. Vol. 65, 397-404 p.
Keyword [en]
Chlamydophila pneumoniae, Chlamydia trachomatis, pre-clinical pharmacokinetics, type III secretion inhibitor, vaginal microbicide, virulence inhibitor
National Category
Pharmacology and Toxicology
URN: urn:nbn:se:umu:diva-56341DOI: 10.1038/ja.2012.43PubMedID: 22669447OAI: diva2:533727
Available from: 2012-06-14 Created: 2012-06-14 Last updated: 2013-01-31Bibliographically approved

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Ur-Rehman, TofeeqDahlgren, Markus KZetterström, Caroline EElofsson, MikaelGylfe, Åsa
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ReferencesLink to record
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