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doi:10.22028/D291-39233
Titel: | Anti-biofilm Agents against Pseudomonas aeruginosa : A Structure-Activity Relationship Study of C-Glycosidic LecB Inhibitors |
VerfasserIn: | Sommer, Roman Rox, Katharina Wagner, Stefanie Hauck, Dirk Henrikus, Sarah S. Newsad, Shelby Arnold, Tatjana Ryckmans, Thomas Brönstrup, Mark Imberty, Anne Varrot, Annabelle Hartmann, Rolf W. Titz, Alexander |
Sprache: | Englisch |
Titel: | Journal of Medicinal Chemistry |
Bandnummer: | 62 |
Heft: | 20 |
Seiten: | 9201-9216 |
Verlag/Plattform: | American Chemical Society |
Erscheinungsjahr: | 2019 |
Freie Schlagwörter: | Biofilms Ligands Reaction products Sulfones Thiophenes |
DDC-Sachgruppe: | 500 Naturwissenschaften |
Dokumenttyp: | Journalartikel / Zeitschriftenartikel |
Abstract: | 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 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. |
DOI der Erstveröffentlichung: | 10.1021/acs.jmedchem.9b01120 |
URL der Erstveröffentlichung: | https://doi.org/10.1021/acs.jmedchem.9b01120 |
Link zu diesem Datensatz: | urn:nbn:de:bsz:291--ds-392339 hdl:20.500.11880/35355 http://dx.doi.org/10.22028/D291-39233 |
ISSN: | 1520-4804 0022-2623 |
Datum des Eintrags: | 6-Mär-2023 |
Bezeichnung des in Beziehung stehenden Objekts: | Supporting Information |
In Beziehung stehendes Objekt: | https://pubs.acs.org/doi/suppl/10.1021/acs.jmedchem.9b01120/suppl_file/jm9b01120_si_001.pdf https://pubs.acs.org/doi/suppl/10.1021/acs.jmedchem.9b01120/suppl_file/jm9b01120_si_002.csv |
Fakultät: | NT - Naturwissenschaftlich- Technische Fakultät |
Fachrichtung: | NT - Chemie NT - Pharmazie |
Professur: | NT - Prof. Dr. Rolf W. Hartmann NT - Univ.-Prof. Dr. phil. Alexander Titz |
Sammlung: | SciDok - Der Wissenschaftsserver der Universität des Saarlandes |
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