2. Academic Validation
  3. Design, synthesis and biological evaluation of dihydrofurocoumarin derivatives as potent neuraminidase inhibitors

Design, synthesis and biological evaluation of dihydrofurocoumarin derivatives as potent neuraminidase inhibitors

  • Bioorg Med Chem Lett. 2021 Apr 1;37:127839. doi: 10.1016/j.bmcl.2021.127839.
Zhi Jian Zhong 1,  Li Ping Cheng 2,  Wan Pang 3,  Xue Song Zheng 1,  Shi Kai Fu 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: chengliping@sit.edu.cn.
  • 3 School of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai 201418, China. Electronic address: pangwan@sit.edu.cn.
PMID: 33556571 DOI: 10.1016/j.bmcl.2021.127839
Abstract

Neuraminidase (NA) is a promising target for development of anti-influenza drugs. In this study a dihydrofurocoumarin derivative ZINC05577497 was discovered as a lead NA inhibitor based on docking-based virtual screening technique. The optimization of lead ZINC05577497 led to the discovery of a series of novel NA inhibitors 5a-5j. Compound 5b has the most potent activity against NA with IC50 = 0.02 µM, which is lower than those of the reference oseltamivir carboxylate (OSC) (IC50 = 0.04 µM) and ZINC05577497 (IC50 = 0.11 µM). Other target compounds also show potential inhibition of NA activity. Molecular docking results indicate that the good potency of 5b may be attributed to the elongation of the dihydrofurocoumarin ring to the 150-cavity. The results of this paper will be useful to discover more potent NA inhibitors.

Keywords

Dihydrofurocoumarin derivatives; Molecule docking; Neuraminidase inhibitors; Virtual screening.

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