Τίτλος:
Catechol-based inhibitors of bacterial urease
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Targeted covalent inhibitors of urease were developed on the basis of the catechol structure. Forty amide and ester derivatives of 3,4-dihydroxyphenylacetic acid, caffeic acid, ferulic acid and gallic acid were obtained and screened against Sporosarcinia pasteurii urease. The most active compound, namely propargyl ester of 3,4-dihydroxyphenylacetic acid exhibited IC 50 = 518 nM andk inact /K i = 1379 M −1 s −1 . Inhibitory activity of this compound was better and toxicity lower than those obtained for the starting compound – catechol. The molecular modelling studies revealed a mode of binding consistent with structure-activity relationships. © 2019 Elsevier Ltd
Συγγραφείς:
Pagoni, A.
Daliani, T.
Macegoniuk, K.
Vassiliou, S.
Berlicki, Ł.
Περιοδικό:
Bioorganic and Medicinal Chemistry Letters
Εκδότης:
Elsevier Ireland Ltd
Λέξεις-κλειδιά:
3,4 dihydroxyphenylacetic acid; caffeic acid; catechol; catechol based bacterial urease inhibitor; ferulic acid; gallic acid; unclassified drug; urease inhibitor; antiinfective agent; catechol derivative; enzyme inhibitor; urease, animal cell; Article; controlled study; drug binding; drug screening; drug structure; fibroblast; IC50; mouse; nonhuman; Sporosarcina pasteurii; structure activity relation; chemistry; drug effect; enzymology; gene expression regulation; molecular docking; molecular model; protein conformation; Sporosarcina, Anti-Bacterial Agents; Catechols; Enzyme Inhibitors; Gene Expression Regulation, Bacterial; Models, Molecular; Molecular Docking Simulation; Protein Conformation; Sporosarcina; Structure-Activity Relationship; Urease
DOI:
10.1016/j.bmcl.2019.02.032
