2. Academic Validation
  3. Design, synthesis, and in vitro biological evaluation of 1H-1,2,3-triazole-4-carboxamide derivatives as new anti-influenza A agents targeting virus nucleoprotein

Design, synthesis, and in vitro biological evaluation of 1H-1,2,3-triazole-4-carboxamide derivatives as new anti-influenza A agents targeting virus nucleoprotein

  • J Med Chem. 2012 Mar 8;55(5):2144-53. doi: 10.1021/jm2013503.
Huimin Cheng 1,  Junting Wan,  Meng-I Lin,  Yingxue Liu,  Xiaoyun Lu,  Jinsong Liu,  Yong Xu,  Jianxin Chen,  Zhengchao Tu,  Yih-Shyun E Cheng,  Ke Ding
Affiliations

Affiliation

  • 1 Key Laboratory of Regenerative Biology and Institute of Chemical Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 190 Kaiyuan Avenue, Guangzhou 510530, People's Republic of China.
PMID: 22332894 DOI: 10.1021/jm2013503
Abstract

The Influenza Virus Nucleoprotein (NP) is an emerging target for anti-influenza drug development. Nucleozin (1) and its closely related derivatives had been identified as NP inhibitors displaying anti-influenza activity. Utilizing 1 as a lead molecule, we successfully designed and synthesized a series of 1H-1,2,3-triazole-4-carboxamide derivatives as new anti-influenza A agents. One of the most potent compounds, 3b, inhibited the replication of various H3N2 and H1N1 influenza A virus strains with IC(50) values ranging from 0.5 to 4.6 μM. Compound 3b also strongly inhibited the replication of H5N1 (RG14), amantidine-resistant A/WSN/33 (H1N1), and oseltamivir-resistant A/WSN/1933 (H1N1, 274Y) virus strains with IC(50) values in sub-μM ranges. Further computational studies and mechanism investigation suggested that 3b might directly target Influenza Virus A nucleoprotein to inhibit its nuclear accumulation.

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