Virtual screening and high-throughput testing of L1 metallo-β-lactamase inhibitor

doi:10.5246/jcps.2021.10.068

Abstract

Abstract:

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%).

Key words: L1, Metallo-beta-lactamase inhibitor, Virtual screening, High-throughput screening

Supporting:

Chennan Liu, Qian Wang, Jiangxue Han, Sihan Liu, Chunling Xiao, Yan Guan, Xinghua Li, Ying Wang, Xiao Wang, Jianzhou Meng, Maoluo Gan, Yishuang Liu. Virtual screening and high-throughput testing of L1 metallo-β-lactamase inhibitor[J]. Journal of Chinese Pharmaceutical Sciences, 2021, 30(10): 806-812.

Figures/Tables 9

Table 1. Top 10 compounds from DS CDOCKER.

Table 2. Top 10 compounds from Sybyl-x 2.0 virtual screening.

Table 3. Top 10 compounds from Smina virtual screening.

Table 4. Top 10 compounds from Schrodinger structure-based virtual screening.

Table 5. The parameters of the L1 testing model 1–36.

Table 6. The evaluation of the L1 testing model 35.

Table 7. Comparison of program accuracy of L1 virtual screening.

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