Application of dithiocarbamate derivative to antibacterial field

Abstract

The invention belongs to the field of medicine chemistry, and discloses application of dithiocarbamate derivative to the antibacterial field. By adopting the compound, the sensitivity of enterobacteriaceae bacteria containing metal beta-lactamase to carbapenems antibiotics can be recovered. In vitro antibacterial experimental result proves that the compound is combined with meropenem (MEM), so that the drug sensitivity of the MEM can be improved. For carbapenems-tolerant NDM-1 enzyme-produced escherichia coli, by adopting the compound, an MIC (minimum inhibitory concentration) value of the carbapenems meropenem can be reduced, optimally by about 40960 times. An experiment on the sensitivity of zinc ions preliminarily proves that the zinc ions have interference on recovery of an MEM drug effect by utilizing the compound. The dynamic germicidal efficacy proves that the germicidal efficacy of the compound to MEM also can be greatly promoted under a combination effect. An in vitro red cytotoxicity experiment and a cytotoxicity experiment prove that the toxicity of the compound is lower, and therefore, the compound is relatively safe. The compound can be used as a candidate medicine of a novel metal beta-lactamase inhibitor.

Description

technical field [0001] The invention belongs to the technical field of medicinal chemistry, and relates to the application of amino dithioformate derivatives as novel metallo-beta-lactamase inhibitors in the antibacterial field. Background technique [0002] The trend of Antimicrobial resistance (AMR) has invaded the world like a ghost (Microbiology and Molecular Biology Reviews 2010, 74, 417.). Antibiotic resistance has become a major threat to public health security (Nature Reviews Microbiology 2015, 13, 42.). The reasons for bacterial drug resistance can be attributed to two aspects: bacterial chromosomal mutation and horizontal transmission of drug resistance genes. Among them, the inherent drug resistance of bacteria is the instinct of bacteria themselves. The acquired drug resistance (Nature 2004, 430, 242.) caused by the horizontal transmission of drug resistance genes is an important reason for the dissemination of drug resistance and the emergence of multi-drug re...

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Problems solved by technology

In 2015, Yang Kewu's research group at Northwest University reported a series of thioglycolic acid thioester amino acid derivatives, whose IC for metallo-β-lactamase L1 50 The minimum can reach 18nM, but its in vitro activity test pro

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