Synthesis of new carolacton derivatives and their activity against biofilms of oral bacteria.

2.50
Hdl Handle:
http://hdl.handle.net/10033/578996
Title:
Synthesis of new carolacton derivatives and their activity against biofilms of oral bacteria.
Authors:
Stumpp, N; Premnath, P; Schmidt, T; Ammermann, J; Dräger, G; Reck, M; Jansen, R; Stiesch, M; Wagner-Döbler, I; Kirschning, A
Abstract:
Carolacton, a secondary metabolite isolated from the extracts of Sorangium cellulosum, causes membrane damage and cell death in biofilms of the caries- and endocarditis-associated bacterium Streptococcus mutans. Here, we report the total synthesis of several derivatives of carolacton. All new structural modifications introduced abolished its biological activity, including subtle ones, such as inversion of configuration at C9. However, a bicyclic bislactone derivative as well as the methyl ester of carolacton resulted in compounds with prodrug properties. Their inhibitory activity on S. mutans was proven to be based on enzymatic hydrolysis by S. mutans which provided native carolacton resulting in biofilm damage in vivo. Moreover, we demonstrate that carolacton acts also on S. gordonii, S. oralis and the periodontitis pathogen Aggregatibacter actinomycetemcomitans, causing elongated cells and growth inhibition.
Affiliation:
Helmholtz Centre for infection research, Inhoffenstr. 7, D-38124 Braunschweig, Germany
Citation:
Synthesis of new carolacton derivatives and their activity against biofilms of oral bacteria. 2015, 13 (20):5765-74 Org. Biomol. Chem.
Journal:
Organic & biomolecular chemistry
Issue Date:
28-May-2015
URI:
http://hdl.handle.net/10033/578996
DOI:
10.1039/c5ob00460h
PubMed ID:
25902328
Type:
Article
Language:
en
ISSN:
1477-0539
Appears in Collections:
publications of the department of microbial drugs (MWIS)

Full metadata record

DC FieldValue Language
dc.contributor.authorStumpp, Nen
dc.contributor.authorPremnath, Pen
dc.contributor.authorSchmidt, Ten
dc.contributor.authorAmmermann, Jen
dc.contributor.authorDräger, Gen
dc.contributor.authorReck, Men
dc.contributor.authorJansen, Ren
dc.contributor.authorStiesch, Men
dc.contributor.authorWagner-Döbler, Ien
dc.contributor.authorKirschning, Aen
dc.date.accessioned2015-10-01T13:18:42Zen
dc.date.available2015-10-01T13:18:42Zen
dc.date.issued2015-05-28en
dc.identifier.citationSynthesis of new carolacton derivatives and their activity against biofilms of oral bacteria. 2015, 13 (20):5765-74 Org. Biomol. Chem.en
dc.identifier.issn1477-0539en
dc.identifier.pmid25902328en
dc.identifier.doi10.1039/c5ob00460hen
dc.identifier.urihttp://hdl.handle.net/10033/578996en
dc.description.abstractCarolacton, a secondary metabolite isolated from the extracts of Sorangium cellulosum, causes membrane damage and cell death in biofilms of the caries- and endocarditis-associated bacterium Streptococcus mutans. Here, we report the total synthesis of several derivatives of carolacton. All new structural modifications introduced abolished its biological activity, including subtle ones, such as inversion of configuration at C9. However, a bicyclic bislactone derivative as well as the methyl ester of carolacton resulted in compounds with prodrug properties. Their inhibitory activity on S. mutans was proven to be based on enzymatic hydrolysis by S. mutans which provided native carolacton resulting in biofilm damage in vivo. Moreover, we demonstrate that carolacton acts also on S. gordonii, S. oralis and the periodontitis pathogen Aggregatibacter actinomycetemcomitans, causing elongated cells and growth inhibition.en
dc.language.isoenen
dc.titleSynthesis of new carolacton derivatives and their activity against biofilms of oral bacteria.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection research, Inhoffenstr. 7, D-38124 Braunschweig, Germanyen
dc.identifier.journalOrganic & biomolecular chemistryen

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