Azolylthioacetamides as potential inhibitors of New Delhi metallo-β-lactamase-1 (NDM-1)

Xiao-Long Liu; Yang Xiang; Cheng Chen; Ke-Wu Yang

doi:10.1038/s41429-018-0121-4

Azolylthioacetamides as potential inhibitors of New Delhi metallo-β-lactamase-1 (NDM-1)

J Antibiot (Tokyo). 2019 Feb;72(2):118-121. doi: 10.1038/s41429-018-0121-4. Epub 2018 Nov 19.

Authors

Xiao-Long Liu^{1

2}, Yang Xiang^{1

3}, Cheng Chen¹, Ke-Wu Yang⁴

Affiliations

¹ Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education, Chemical Biology Innovation Laboratory, College of Chemistry and Materials Science, Northwest University, Xi'an, 710127, P. R. China.
² Medical College, Yan'an University, Yan'an, 716000, P. R. China.
³ College of Physical Education, Yan'an University, Yan'an, 716000, P. R. China.
⁴ Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education, Chemical Biology Innovation Laboratory, College of Chemistry and Materials Science, Northwest University, Xi'an, 710127, P. R. China. [email protected].

PMID: 30449891
DOI: 10.1038/s41429-018-0121-4

Abstract

Thirteen azolylthioacetamides was synthesized and characterized. Biological activity assays with MβLs revealed that all of these compounds (except 3 and 6) gained exhibited inhibitory activity on NDM-1, with an IC₅₀ value ranging from 3.8 to 26.4 μM. Inhibitors 11 and 13, in combination with cefazolin, resulted in a four-fold decrease in MIC of the antibiotic against Escherichia coli cells expressing NDM-1. Docking studies revealed that the inhibitors 7, 9, and 13 bound to active site of NDM-1.

MeSH terms

Acetamides / chemical synthesis
Acetamides / pharmacology*
Anti-Bacterial Agents / pharmacology*
Cefazolin / pharmacology*
Escherichia coli / genetics
Escherichia coli / metabolism*
Microbial Sensitivity Tests
beta-Lactamases / metabolism*

Substances

Acetamides
Anti-Bacterial Agents
beta-Lactamases
beta-lactamase NDM-1
Cefazolin