Dithiocarbamates: Efficient metallo-β-lactamase inhibitors with good antibacterial activity when combined with meropenem.

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ID: 95434
2018
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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.
Reference Key
wang2018dithiocarbamatesbioorganic Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Wang, Ming-Ming;Chu, Wen-Chao;Yang, Yi;Yang, Qian-Qian;Qin, Shang-Shang;Zhang, En;
Journal Bioorganic & medicinal chemistry letters
Year 2018
DOI
S0960-894X(18)30759-5
URL
Keywords
antibiotic resistance antibacterial activity meropenem dithiocarbamates metallo-β-lactamase inhibitors

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