2. Academic Validation
  3. Imidazole-based pinanamine derivatives: Discovery of dual inhibitors of the wild-type and drug-resistant mutant of the influenza A virus

Imidazole-based pinanamine derivatives: Discovery of dual inhibitors of the wild-type and drug-resistant mutant of the influenza A virus

  • Eur J Med Chem. 2016 Jan 27:108:605-615. doi: 10.1016/j.ejmech.2015.12.013.
Jianghong Dong 1,  Shengwei Chen 1,  Runfeng Li 2,  Wei Cui 1,  Haiming Jiang 2,  Yixia Ling 1,  Zifeng Yang 2,  Wenhui Hu 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 190 Kaiyuan Avenue, Guangzhou 510530, China.
  • 2 State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
  • 3 State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 190 Kaiyuan Avenue, Guangzhou 510530, China. Electronic address: hu_wenhui@gibh.ac.cn.
PMID: 26722757 DOI: 10.1016/j.ejmech.2015.12.013
Abstract

We previously reported potent hit compound 4 inhibiting the wild-type influenza A virus A/HK/68 (H3N2) and A/M2-S31N mutant viruses A/WS/33 (H1N1), with its latter activity quite weak. To further increase its potency, a structure-activity relationship study of a series of imidazole-linked pinanamine derivatives was conducted by modifying the imidazole ring of this compound. Several compounds of this series inhibited the amantadine-sensitive virus at low micromolar concentrations. Among them, 33 was the most potent compound, which was identified as being active on an amantadine-sensitive virus through blocking of the viral M2 ion channel. Furthermore, 33 markedly inhibited the amantadine-resistant virus (IC50 = 3.4 μM) and its activity increased by almost 24-fold compared to initial compound, with its action mechanism being not M2 channel mediated.

Keywords

Dual inhibitory activity; Influenza A virus; M2 ion channel; Pinanamine derivatives.

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