-Aryl-3-mercaptosuccinimides as Antivirulence Agents Targeting Pseudomonas aeruginosa Elastase and Clostridium Collagenases.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Kany, Andreas M
Berger, Fabian K
Hartmann, Rolf W
Hirsch, Anna K H
MetadataShow full item record
AbstractIn 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.
CitationJ Med Chem. 2020 Aug 13;63(15):8359-8368. doi: 10.1021/acs.jmedchem.0c00584. Epub 2020 Jun 17. PMID: 32470298.
AffiliationHIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.
JournalJournal of medicinal chemistry
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-ShareAlike 4.0 International
- Binding Mode Characterization and Early in Vivo Evaluation of Fragment-Like Thiols as Inhibitors of the Virulence Factor LasB from Pseudomonas aeruginosa.
- Authors: Kany AM, Sikandar A, Haupenthal J, Yahiaoui S, Maurer CK, Proschak E, Köhnke J, Hartmann RW
- Issue date: 2018 Jun 8
- Structures of three polycystic kidney disease-like domains from Clostridium histolyticum collagenases ColG and ColH.
- Authors: Bauer R, Janowska K, Taylor K, Jordan B, Gann S, Janowski T, Latimer EC, Matsushita O, Sakon J
- Issue date: 2015 Mar
- Discovery of a Potent Inhibitor Class with High Selectivity toward Clostridial Collagenases.
- Authors: Schönauer E, Kany AM, Haupenthal J, Hüsecken K, Hoppe IJ, Voos K, Yahiaoui S, Elsässer B, Ducho C, Brandstetter H, Hartmann RW
- Issue date: 2017 Sep 13
- Novel inhibitors of the Pseudomonas aeruginosa virulence factor LasB: a potential therapeutic approach for the attenuation of virulence mechanisms in pseudomonal infection.
- Authors: Cathcart GR, Quinn D, Greer B, Harriott P, Lynas JF, Gilmore BF, Walker B
- Issue date: 2011 Jun
- Gene duplication and multiplicity of collagenases in Clostridium histolyticum.
- Authors: Matsushita O, Jung CM, Katayama S, Minami J, Takahashi Y, Okabe A
- Issue date: 1999 Feb