Design, synthesis and biological evaluation of 1,3,4-triazole-3-acetamide derivatives as potent neuraminidase inhibitors

  • Bioorg Med Chem Lett. 2022 Apr 1;61:128590. doi: 10.1016/j.bmcl.2022.128590.
Lin Shi  1 ,  Xing Yong Zhang  1 ,  Li Ping Cheng  2
Affiliations
  • 1. School of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai 201418, China.
  • 2. School of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai 201418, China. Electronic address: [email protected].
PMID: 35108623 DOI: 10.1016/j.bmcl.2022.128590
Abstract

Neuraminidase (NA) is an ideal target for the development of anti-influenza drugs. In this paper, ZINC06057848 was screened out as a hit compound by docking-based virtual screening and molecular dynamics (MD) simulation. The modification and optimization of hit ZINC06057848 resulted in the discovery of a series of novel 1,3,4-triazole-containing NA inhibitors (5a-5j). Compound 5c exerts the best inhibitory activity (IC50 = 0.11 µM) against NA, which is comparable to the positive control oseltamivir carboxylate (OSC) (IC50 = 0.10 µM). Molecular docking analysis indicates that the good efficacy of inhibitor 5c may be attributed to the furan and triazole rings extending into 430-cavity and the ethylbenzene part occupying the active site. The results of this work may help in the development of new NA inhibitors.

Keywords
430-cavity; Influenza; Neuraminidase inhibitors; Triazole derivatives; Virtual screening.
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