2. Academic Validation
  3. Design, synthesis and biological evaluation of novel 1, 3, 4-oxadiazole derivatives as potent neuraminidase inhibitors

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

  • Bioorg Med Chem. 2022 Mar 1;57:116647. doi: 10.1016/j.bmc.2022.116647.
Wei Yu 1,  Li Ping Cheng 2,  Wan Pang 1,  Ling Ling Guo 1
Affiliations

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: 35121400 DOI: 10.1016/j.bmc.2022.116647
Abstract

Neuraminidase (NA) is an important target in the development of anti-influenza virus drugs. Compounds containing 1,3, 4-oxadiazole heterocycles have good biological activity and have been proved to have wide applications in Antibacterial and Antiviral drugs. In this paper, a series of novel 1, 3, 4-oxadiazole neuraminidase inhibitors (6a-6l) were designed and synthesized and their inhibitory activities of NA was tested in vitro. The results displayed that compound 6d exerts the best inhibitory activity (IC50 = 0.027 µM), which was obviously lower than that of oseltamivir carboxylate (OSC) (IC50 = 0.082 µM). Molecular docking analysis showed that the 1, 3, 4-oxadiazole heterocycle plays crucial part in compound 6d, and it can interact with the key arginine triad (Arg118, Arg292 and Arg 371) at the NA S1 site. The good efficacy of 6d may also be attributed to the extension of the substituted aniline ring to the 150-cavitiy. The theoretical and experimental results may provide reference for development of new anti-influenza drugs.

Keywords

1, 3, 4-oxadiazole; 150-cavity; 430-cavity; Bioassay; Neuraminidase inhibitor.

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