Metal [beta]-lactamase inhibitor cyclo-amidodithioformate derivative and preparation method of same

Abstract

The invention belongs to the field of medical chemistry and discloses a metal [beta]-lactamase inhibitor cyclo-amidodithioformate derivative and a preparation method of the same. The compound is represented as the structural formulas 1, 2 or 3 as follows, wherein R is sodium, a methyl group, an n-hexyl group, an n-decyl group or an n-dodecyl group. The inhibitor is combined with a carbapenem antibiotic (e.g. meropenem) to achieve the inhibition activity of metal [beta]-lactamase, so that the sensitivity to the carbapenem antibiotic of a bacterial strain having drug resistance against the carbapenem is recovered. The inhibitor has significant effects on a bacterial strain producing NDM-1 enzyme and having drug resistance against the carbapenem. A red blood cell haemolytic test and a cytotoxicity test prove that the compound is low in toxicity. The series of the compounds is hopeful to serve as a potential candidate medicine of the metal [beta]-lactamase inhibitor.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and relates to a metal β-lactamase inhibitor cyclic aminodithioformate derivative with potential application value and a preparation method thereof. Background technique [0002] Since the use of antibiotics in the clinical treatment of bacterial infections, the problem of bacterial resistance has become increasingly serious. There are many reasons for bacterial drug resistance, among which drug hydrolytic enzymes that can spread horizontally are an important reason for bacteria to acquire drug resistance. In 2009, the first superbacteria producing NDM-1 metallo-β-lactamase was discovered in New Delhi, India. This bacterium is only sensitive to a few antibacterial drugs such as colistin, has a wide spectrum of drug resistance, and is difficult to treat (The Lancet Infectious Diseases 2010, 10, 597.). Since the discovery of the NDM-1 enzyme-producing strain, it has been prevalent in more than ...

AI Technical Summary

Problems solved by technology

In 2009, the first superbacteria producing NDM-1 metallo-β-lactamase was discovered in New Delhi, India. This bacterium is only sensitive to a few antibacterial drugs such as colistin, has a wide spectrum of drug resistance, and is difficult to treat (The Lancet Infectious Diseases2010, 10, 597.)

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 experiments show that this type of compound is not effective in restoring the sensitivity of drug-resistant strains to meropenem (Acs Medicinal Chemistry Letters 2015,6,660.)

Images