ACTA VETERINARIA ET ZOOTECHNICA SINICA ›› 2018, Vol. 49 ›› Issue (7): 1500-1510.doi: 10.11843/j.issn.0366-6964.2018.07.020

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Virtual Screening and Activity Evaluation of Multi-target Antibacterial Lead Compounds

CAI Jun-jun, YUAN Tian-qing, YANG Yin-ping, GAO Shuang, GONG Xing-wen*   

  1. School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou 310018, China
  • Received:2017-09-29 Online:2018-07-23 Published:2018-07-19

Abstract:

Pseudomonas aeruginosa and Escherichia coli are two kinds of common pathogenic bacteria existed extensively in hospitals and veterinary clinics. They can infect both human and animals and brought great challenges to disease treatment and economic development. In order to obtain novel lead compounds targeting to penicillin-binding proteins(PBPs) of P. aerμginosa and E. coli, molecular docking was performed using UCSF DOCK 6.5 against ZINC database. PBP3 of Pseudomonas aeruginosa and PBP1b, PBP4, and PBP5 of Escherichia coli were chosen as the docking targets. Lead compounds with high scores and novel structures were selected for organic synthesis. Their antibacterial activities were evaluated according to their minimum inhibitory concentrations(MIC). Grid score was used for the first round of virtual screening, while lead compounds with grid scores lower than -125.6 kJ·mol-1 were subjected to second round of screening. Amber score was used for the second round of virtual screening. Finally, approximately 200 compounds with amber score lower than -83.7 kJ·mol-1 were screened out. In view of the structural novelty, lead compound ZINC00053282 was selected for synthesis. The result of antibacterial assay indicated that it could inhibit both Gram-positive and Gram-negative bacteria, with an activity better than sulfadiazine. These results mean that this lead compound is an potential antibacterial drug and might be used to solve the drug resistance problem.

Key words: Pseudomonas aeruginosa, Escherichia coli, penicillin-binding protein, drug resistance, virtual screening

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