Anti-influenza drug discovery: Structure-activity relationship and mechanistic insight into novel angelicin derivatives

Jiann Yih Yeh, Mohane Selvaraj Coumar, Jim Tong Horng, Hui Yi Shiao, Fu Ming Kuo, Hui Ling Lee, In Chun Chen, Chun Wei Chang, Wen Fang Tang, Sung Nain Tseng, Chi Jene Chen, Shin Ru Shih, John T.A. Hsu, Chun Chen Liao, Yu Sheng Chao, Hsing Pang Hsieh

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151 Citations (Scopus)


By using a cell-based high throughput screening campaign, a novel angelicin derivative 6a was identified to inhibit influenza A. (H1N1) virus induced cytopathic effect in Madin-Darby canine kidney cell culture in low micromolar range. Detailed structure-activity relationship studies of 6a revealed that the angelicin scaffold is essential for activity in pharmacophore B, while meta-substituted phenyl/2-thiophene rings are optimal in pharmacophore A and C. The optimized lead 4-methyl-9-phenyl-8-(thiophene-2-carbonyl)-furo[2,3-h] chromen-2-one (8g, IC50 = 70 nM) showed 64-fold enhanced activity compared to the high throughput screening (HTS) hit 6a. Also, 8g was found effective in case of influenza A (H3N2) and influenza B virus strains similar to approved anti-influenza drug zanamivir (4). Preliminary mechanistic studies suggest that these compounds act as anti-influenza agents by inhibiting ribonucleoprotein (RNP) complex associated activity and have the potential to be developed further, which could form the basis for developing additional defense against influenza pandemics.

Original languageEnglish
Pages (from-to)1519-1533
Number of pages15
JournalJournal of Medicinal Chemistry
Issue number4
Publication statusPublished - 2010 Feb 25

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery


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