2. Academic Validation
  3. Design, synthesis and biological evaluation of oseltamivir derivatives containing pyridyl group as potent inhibitors of neuraminidase for influenza A

Design, synthesis and biological evaluation of oseltamivir derivatives containing pyridyl group as potent inhibitors of neuraminidase for influenza A

  • Eur J Med Chem. 2020 Jan 1;185:111841. doi: 10.1016/j.ejmech.2019.111841.
Kuanglei Wang 1,  Zaiqiang Lei 2,  Lei Zhao 3,  Binfeng Chen 2,  Fei Yang 2,  Kemin Liu 2,  Hongxi Zhu 2,  Hongqian Zhao 2,  Ruiyuan Cao 4,  Kun Zhang 5,  Yongshou Tian 6
Affiliations

Affiliations

  • 1 School of Biotechnology and Health Sciences, Wuyi University, Jiangmen, 529020, PR China; International Healthcare Innovation Institute (Jiangmen), Jiangmen, 529040, PR China; School of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, 510006, PR China.
  • 2 Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, 110016, PR China.
  • 3 National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, PR China.
  • 4 National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, PR China. Electronic address: [email protected].
  • 5 School of Biotechnology and Health Sciences, Wuyi University, Jiangmen, 529020, PR China; International Healthcare Innovation Institute (Jiangmen), Jiangmen, 529040, PR China; School of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, 510006, PR China. Electronic address: [email protected].
  • 6 Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, 110016, PR China. Electronic address: [email protected].
PMID: 31708183 DOI: 10.1016/j.ejmech.2019.111841
Abstract

Influenza A neuraminidase plays an indispensable role in the process of replication and transmission of influenza, so the neuraminidase inhibition can prevent the reproduction of the viruses therefore achieve the effect of treatment of influenza. However, drug resistance of neuraminidase inhibitors such as oseltamivir highlights the need to develop novel structural neuraminidase inhibitors. Here we explored a series of oseltamivir derivatives bearing pyridyl group. Among them, compound 23b exhibiting potent inhibitory activity against neuraminidase from H5N1 subtype was comparable to oseltamivir carboxylate. Cytopathic effect inhibition assay in MDCK cells indicated that compound 23b exerted powerful inhibitions on influenza viruses. And compound 23b were nontoxic to MDCK cells. Meanwhile, compound 23b showed high stability towards rat liver microsomes, human liver microsomes and human plasma. This research enriched the structural type of neuraminidase inhibitors.

Keywords

150 cavity; Influenza virus; Neuraminidase inhibitors; Oseltamivir analogues.

Figures
Products