Anti-biofilm Agents against Pseudomonas aeruginosa: A Structure-Activity Relationship Study of C-Glycosidic LecB Inhibitors
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
Henrikus, Sarah S
Hartmann, Rolf W
MetadataShow full item record
AbstractBiofilm formation is a key mechanism of antimicrobial resistance. We have recently reported two classes of orally bioavailable C-glycosidic inhibitors of the Pseudomonas aeruginosa lectin LecB with antibiofilm activity. They proved efficient in target binding, were metabolically stable, nontoxic, selective, and potent in inhibiting formation of bacterial biofilm. Here, we designed and synthesized six new carboxamides and 24 new sulfonamides for a detailed structure-activity relationship for two clinically representative LecB variants. Sulfonamides generally showed higher inhibition compared to carboxamides, which was rationalized based on crystal structure analyses. Substitutions at the thiophenesulfonamide increased binding through extensive contacts with a lipophilic protein patch. These metabolically stable compounds showed a further increase in potency toward the target and in biofilm inhibition assays. In general, we established the structure-activity relationship for these promising antibiofilm agents and showed that modification of the sulfonamide residue bears future optimization potential.
CitationJ Med Chem. 2019 Oct 24;62(20):9201-9216. doi: 10.1021/acs.jmedchem.9b01120. Epub 2019 Oct 11.
AffiliationHIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
PublisherAmerican Chemical Society
JournalJournal of medicinal Chemistry
The following license files are associated with this item:
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-ShareAlike 4.0 International
- Cinnamide Derivatives of d-Mannose as Inhibitors of the Bacterial Virulence Factor LecB from Pseudomonas aeruginosa.
- Authors: Sommer R, Hauck D, Varrot A, Wagner S, Audfray A, Prestel A, Möller HM, Imberty A, Titz A
- Issue date: 2015 Dec
- Synthesis of mannoheptose derivatives and their evaluation as inhibitors of the lectin LecB from the opportunistic pathogen Pseudomonas aeruginosa.
- Authors: Hofmann A, Sommer R, Hauck D, Stifel J, Göttker-Schnetmann I, Titz A
- Issue date: 2015 Aug 14
- Glycomimetic, Orally Bioavailable LecB Inhibitors Block Biofilm Formation of Pseudomonas aeruginosa.
- Authors: Sommer R, Wagner S, Rox K, Varrot A, Hauck D, Wamhoff EC, Schreiber J, Ryckmans T, Brunner T, Rademacher C, Hartmann RW, Brönstrup M, Imberty A, Titz A
- Issue date: 2018 Feb 21
- Discovery of two classes of potent glycomimetic inhibitors of Pseudomonas aeruginosa LecB with distinct binding modes.
- Authors: Hauck D, Joachim I, Frommeyer B, Varrot A, Philipp B, Möller HM, Imberty A, Exner TE, Titz A
- Issue date: 2013 Aug 16
- Overcoming antibiotic resistance in <i>Pseudomonas aeruginosa</i> biofilms using glycopeptide dendrimers.
- Authors: Michaud G, Visini R, Bergmann M, Salerno G, Bosco R, Gillon E, Richichi B, Nativi C, Imberty A, Stocker A, Darbre T, Reymond JL
- Issue date: 2016 Jan 1