2. Academic Validation
  3. Synthesis and biological evaluation of NH2-acyl oseltamivir analogues as potent neuraminidase inhibitors

Synthesis and biological evaluation of NH2-acyl oseltamivir analogues as potent neuraminidase inhibitors

  • Eur J Med Chem. 2017 Dec 1;141:648-656. doi: 10.1016/j.ejmech.2017.10.004.
Kuanglei Wang 1,  Fei Yang 1,  Lihui Wang 2,  Kemin Liu 1,  Lu Sun 3,  Bin Lin 1,  Yaping Hu 1,  Boyu Wang 1,  Maosheng Cheng 4,  Yongshou Tian 5
Affiliations

Affiliations

  • 1 Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, PR China.
  • 2 School of Life Sciences and Biopharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, PR China.
  • 3 School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, PR China.
  • 4 Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, PR China. Electronic address: [email protected].
  • 5 Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, PR China. Electronic address: [email protected].
PMID: 29107426 DOI: 10.1016/j.ejmech.2017.10.004
Abstract

Neuraminidase inhibitors can deter nascent viruses from infecting intact cells by preventing their release from host cells. Herein, a neuraminidase inhibitor 11b absent of basic moieties was discovered in the process of searching for inhibitors targeting 150 cavity. It exhibited potent inhibitions against wild-type neuraminidases from group 1 (H5N1 and H1N1) and group 2 (H7N9) subtypes with IC50 values similar to those of oseltamivir carboxylate. Moreover, 11b showed moderate inhibitions against mutant neuraminidases from H5N1-H274Y and H1N1-H274Y with IC50 values of 2075 nM and 1382 nM, which were inferior to those of oseltamivir carboxylate (6095 nM and 4071 nM). The results were not consistent with the recognized SARs that a basic moiety was an indispensable part of a potent inhibitor.

Keywords

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

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