Dithiocarbamates: Efficient metallo-ß-lactamase inhibitors with good antibacterial activity when combined with meropenem.
Bioorg Med Chem Lett
; 28(21): 3436-3440, 2018 11 15.
Article
em En
| MEDLINE
| ID: mdl-30262427
ABSTRACT
The activity of ß-lactam antibiotics is compromised by metallo-ß-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 24â¯h when they were treated with compound 4fâ¯+â¯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.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Tiocarbamatos
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Inibidores de beta-Lactamases
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Meropeném
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Antibacterianos
Limite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2018
Tipo de documento:
Article