(–)-Epicatechin gallate serves as a novel new delhi metallo-β-lactamase-1 (NDM-1) inhibitor

doi:10.5246/jcps.2021.09.059

Abstract

Abstract:

The β-lactam antibiotic resistance caused by NDM-1 has become a major crisis of global public health. We have previously screened out (–)-epicatechin gallate (ECG) as a potent NDM-1 inhibitor. We further discussed its inhibitory effect and action mode in the present study. According to our results, ECG reversibly inactivated NDM-1 in a non-competitive mode, with an IC₅₀ value of 4.48 μM. ECG effectively recovered the activity of several β-lactam antibiotics against resistant strain harboring blaNDM-1. Especially, the effects on carbapenems were worth mentioning. The zinc supplement assay indicated a zinc-related mechanism of ECG. Different from traditional chelating agents, it showed low toxicity both in vivo and in vitro. In a word, our findings provided a promising NDM-1 inhibitor, ECG, which was able to assist carbapenems against NDM-1-producing strain.

Key words: NDM-1, (–)-Epicatechin gallate, Inhibitor, Antibiotics resistance

Supporting:

Qian Wang, Chennan Liu, Jiangxue Han, Sihan Liu, Chunling Xiao, Yan Guan, Xinghua Li, Ying Wang, Xiao Wang, Jianzhou Meng, Maoluo Gan, Yishuang Liu. (–)-Epicatechin gallate serves as a novel new delhi metallo-β-lactamase-1 (NDM-1) inhibitor[J]. Journal of Chinese Pharmaceutical Sciences, 2021, 30(9): 716-724.

Figures/Tables 5

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