Theβ-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 inhi...Theβ-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 4.48μM.ECG effectively recovered the activity of severalβ-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.展开更多
As a zinc-dependent enzyme, metal-β-lactamase L1 contributes to the development of β-lactam antibiotic resistance. The metal-β-lactamase inhibitor can restore the efficacy of β-lactam antibiotics, and its developm...As a zinc-dependent enzyme, metal-β-lactamase L1 contributes to the development of β-lactam antibiotic resistance. The metal-β-lactamase inhibitor can restore the efficacy of β-lactam antibiotics, and its development has attracted much attention. In the present study, we used four widely-used virtual screening programs to screen 7035 small molecules to identify potential L1 inhibitors, and a high-throughput experimental model of L1 inhibitors was established. In this high-throughput testing model, the inhibition rate of 163 compounds on L1 exceeded 40%. The results of virtual screening of 7035 small molecules using the following four programs showed that among the top 1.35% of the compounds, their hit rates were ranked as Schr?dinger’s(5.26%), DS(1.05%), and Sybyl-x 2.0(1.05%), and Smina(2.11%).展开更多
基金Natural Sciences Foundation of China(NSFC,Grant No.81872913)National High-tech R&D Program(863 Program,Grant No.2015AA020911)。
文摘Theβ-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 4.48μM.ECG effectively recovered the activity of severalβ-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.
基金Natural Sciences Foundation of China (Grant No. 81872913)National High-tech R&D Program (863 Program, Grant No. 2015AA020911)。
文摘As a zinc-dependent enzyme, metal-β-lactamase L1 contributes to the development of β-lactam antibiotic resistance. The metal-β-lactamase inhibitor can restore the efficacy of β-lactam antibiotics, and its development has attracted much attention. In the present study, we used four widely-used virtual screening programs to screen 7035 small molecules to identify potential L1 inhibitors, and a high-throughput experimental model of L1 inhibitors was established. In this high-throughput testing model, the inhibition rate of 163 compounds on L1 exceeded 40%. The results of virtual screening of 7035 small molecules using the following four programs showed that among the top 1.35% of the compounds, their hit rates were ranked as Schr?dinger’s(5.26%), DS(1.05%), and Sybyl-x 2.0(1.05%), and Smina(2.11%).
