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Dithiocarbamates: Efficient metallo-β-lactamase inhibitors with good antibacterial activity when combined with meropenem.
- Source :
-
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2018 Nov 15; Vol. 28 (21), pp. 3436-3440. Date of Electronic Publication: 2018 Sep 20. - Publication Year :
- 2018
-
Abstract
- The activity of β-lactam antibiotics is compromised by metallo-β-lactamases (MBLs). Herein, a series of dithiocarbamate derivatives were designed and synthesized. Their antibacterial activities were tested in combination with meropenem (MEM) against several MBL (NDM and IMP type)-producing clinical isolates. Clinical isolates harboring NDM-1 and IMP-4 became susceptible to MEM when it was combined with dithiocarbamate compounds 4a, 4b or 4f synthesized in this work. Compounds 4a and 4b increased the effectiveness of MEM by up to 2560 times against strains. In vitro bactericidal dynamics tests showed that bacteria died within 24 h when they were treated with compound 4f + MEM. Compounds 4a, 4b and 4f were non-hemolytic and exhibited low toxicity toward HeLa cells in vitro. These data show that compounds containing dithiocarbamate functional group may be helpful in the development of MBL inhibitors.<br /> (Copyright © 2018 Elsevier Ltd. All rights reserved.)
- Subjects :
- Anti-Bacterial Agents chemical synthesis
Anti-Bacterial Agents toxicity
Enterobacteriaceae drug effects
Erythrocytes drug effects
HeLa Cells
Hemolysis drug effects
Humans
Microbial Sensitivity Tests
Thiocarbamates chemical synthesis
Thiocarbamates toxicity
Zinc metabolism
beta-Lactamase Inhibitors chemical synthesis
beta-Lactamase Inhibitors toxicity
beta-Lactamases metabolism
Anti-Bacterial Agents pharmacology
Meropenem pharmacology
Thiocarbamates pharmacology
beta-Lactamase Inhibitors pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3405
- Volume :
- 28
- Issue :
- 21
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 30262427
- Full Text :
- https://doi.org/10.1016/j.bmcl.2018.09.028