2. Academic Validation
  3. Discovery of novel thiophene derivatives as potent neuraminidase inhibitors

Discovery of novel thiophene derivatives as potent neuraminidase inhibitors

  • Eur J Med Chem. 2021 Dec 5;225:113762. doi: 10.1016/j.ejmech.2021.113762.
Zhi Jian Zhong 1,  Xiao Tong Hu 2,  Li Ping Cheng 3,  Xing Yong Zhang 1,  Qiang Zhang 4,  Ju Zhang 5
Affiliations

Affiliations

  • 1 School of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai, 201418, China.
  • 2 Unit of Animal Infectious Diseases, State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, Hubei, China.
  • 3 School of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai, 201418, China. Electronic address: [email protected].
  • 4 College of Biomedicine and Health, Huazhong Agricultural University, Wuhan, 430070, Hubei, China. Electronic address: [email protected].
  • 5 Wuhan Yangene Biological Technology Co, LTD, Yuechuang Center of Huazhong Agricultural University, Wuhan, 430070, Hubei, China.
PMID: 34411893 DOI: 10.1016/j.ejmech.2021.113762
Abstract

Neuraminidase (NA) is an important target for the treatment of influenza. In this study, a new lead NA inhibitor, 4 (ZINC01121127), was discovered by pharmacophore-based virtual screening and molecular dynamic (MD) simulation. Some novel NA inhibitors containing thiophene ring were synthesized by optimizing the skeleton of the lead compound 4. Compound 4b had the most potent inhibitory activity against NA (IC50 = 0.03 μM), which was better than the positive control oseltamivir carboxylate (IC50 = 0.06 μM). 4b (EC50 = 1.59 μM) also exhibits excellent Antiviral activity against A/chicken/Hubei/327/2004 (H5N1-DW), which is superior to the reference drug OSC (EC50 = 5.97 μM). Molecular docking study shows that the thiophene moiety plays an essential role in compound 4b, which can bind well to the active site of NA. The good activity of 4b may be also ascribed to the extending of quinoline ring into the 150-cavity. The results of this study may provide an insightful help for the development of new NA inhibitors.

Keywords

150-Cavity; Neuraminidase inhibitor; Thiophene; Virtual screening.

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