Loading...
-Aryl-3-mercaptosuccinimides as Antivirulence Agents Targeting Pseudomonas aeruginosa Elastase and Clostridium Collagenases.
Konstantinović, Jelena Yahiaoui, Samir Alhayek, Alaa Haupenthal, Jörg Schönauer, Esther Andreas, Anastasia Kany, Andreas M Müller, Rolf Koehnke, Jesko Berger, Fabian K
Konstantinović, Jelena
Yahiaoui, Samir
Alhayek, Alaa
Haupenthal, Jörg
Schönauer, Esther
Andreas, Anastasia
Kany, Andreas M
Müller, Rolf
Koehnke, Jesko
Berger, Fabian K
Citations
Altmetric:
Advisors
Editors
Other Contributors
Issue Date
2020-06-17
Submitted date
Files
Loading...
Open Access article
Adobe PDF, 1.95 MB
Other Titles
Abstract
In light of the global antimicrobial-resistance crisis, there is an urgent need for novel bacterial targets and antibiotics with novel modes of action. It has been shown that Pseudomonas aeruginosa elastase (LasB) and Clostridium histolyticum (Hathewaya histolytica) collagenase (ColH) play a significant role in the infection process and thereby represent promising antivirulence targets. Here, we report novel N-aryl-3-mercaptosuccinimide inhibitors that target both LasB and ColH, displaying potent activities in vitro and high selectivity for the bacterial over human metalloproteases. Additionally, the inhibitors demonstrate no signs of cytotoxicity against selected human cell lines and in a zebrafish embryo toxicity model. Furthermore, the most active ColH inhibitor shows a significant reduction of collagen degradation in an ex vivo pig-skin model.
Citation
J Med Chem. 2020 Aug 13;63(15):8359-8368. doi: 10.1021/acs.jmedchem.0c00584. Epub 2020 Jun 17. PMID: 32470298.
Publisher
Journal
PubMed ID
PubMed Central ID
Additional Links
Embedded video
Type
Article
Language
en
Description
Series/Report no.
ISSN
EISSN
1520-4804
ISBN
ISMN
Gov't Doc #
Sponsors
License
Attribution-NonCommercial-ShareAlike 4.0 International