دورية أكاديمية
Anti-biofilm Agents against Pseudomonas aeruginosa : A Structure–Activity Relationship Study of C -Glycosidic LecB Inhibitors
| العنوان: | Anti-biofilm Agents against Pseudomonas aeruginosa : A Structure–Activity Relationship Study of C -Glycosidic LecB Inhibitors |
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| المؤلفون: | Sommer, Roman, Rox, Katharina, Wagner, Stefanie, Hauck, Dirk, Henrikus, Sarah, Newsad, Shelby, Arnold, Tatjana, Ryckmans, Thomas, Brönstrup, Mark, Imberty, Anne, Varrot, Annabelle, Hartmann, Rolf, Titz, Alexander |
| المساهمون: | Chemical Biology of Carbohydrates, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), German Center for Infection Research - partner site Hannover-Braunschweig (DZIF), Roche Innovation Center Basel, Switzerland, Centre de Recherches sur les Macromolécules Végétales (CERMAV ), Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes 2016-2019 (UGA 2016-2019 ), Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Labex Arcane, ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017) |
| المصدر: | ISSN: 0022-2623. |
| بيانات النشر: | HAL CCSD American Chemical Society |
| سنة النشر: | 2019 |
| المجموعة: | Université Grenoble Alpes: HAL |
| مصطلحات موضوعية: | [CHIM]Chemical Sciences, [CHIM.THER]Chemical Sciences/Medicinal Chemistry |
| الوصف: | International audience ; Biofilm 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 anti-biofilm activity. They proved efficient in target binding, were metabolically stable, non-toxic, selective and potent in inhibiting formation of bacterial biofilm. Here, we designed and synthesized 6 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 towards the target and in biofilm inhibition assays. In general, we established the structure-activity relationship for these promising anti-biofilm agents and showed that modification of the sulfonamide residue bears future optimization potential. 1 |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | hal-02349120; https://hal.science/hal-02349120Test; https://hal.science/hal-02349120/documentTest; https://hal.science/hal-02349120/file/20190830-hybrid2-pages9-bib.pages.pdfTest |
| DOI: | 10.1021/acs.jmedchem.9b01120 |
| الإتاحة: | https://doi.org/10.1021/acs.jmedchem.9b01120Test https://hal.science/hal-02349120Test https://hal.science/hal-02349120/documentTest https://hal.science/hal-02349120/file/20190830-hybrid2-pages9-bib.pages.pdfTest |
| حقوق: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.73ABAF1F |
| قاعدة البيانات: | BASE |
| DOI: | 10.1021/acs.jmedchem.9b01120 |
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