Details
| Original language | English |
|---|---|
| Pages (from-to) | 5765-5774 |
| Number of pages | 10 |
| Journal | Organic and Biomolecular Chemistry |
| Volume | 13 |
| Issue number | 20 |
| Publication status | Published - 28 May 2015 |
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.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Biochemistry
- Chemistry(all)
- Physical and Theoretical Chemistry
- Chemistry(all)
- Organic Chemistry
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In: Organic and Biomolecular Chemistry, Vol. 13, No. 20, 28.05.2015, p. 5765-5774.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Synthesis of new carolacton derivatives and their activity against biofilms of oral bacteria
AU - Stumpp, N.
AU - Premnath, P.
AU - Schmidt, Thomas
AU - Ammermann, Jonas
AU - Dräger, Gerald
AU - Reck, M.
AU - Jansen, Rolf
AU - Stiesch, M.
AU - Wagner-Döbler, I.
AU - Kirschning, Andreas
PY - 2015/5/28
Y1 - 2015/5/28
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84929346618&partnerID=8YFLogxK
U2 - 10.1039/c5ob00460h
DO - 10.1039/c5ob00460h
M3 - Article
C2 - 25902328
AN - SCOPUS:84929346618
VL - 13
SP - 5765
EP - 5774
JO - Organic and Biomolecular Chemistry
JF - Organic and Biomolecular Chemistry
SN - 1477-0520
IS - 20
ER -