Synthesis of C-4-modified zanamivir analogs as neuraminidase inhibitors and their anti-AIV activities

Deju Ye, Woo Jin Shin, Ning Li, Wei Tang, Enguang Feng, Jian Li, Pei Lan He, Jian Ping Zuo, Hanjo Kim, Ky Youb Nam, Weiliang Zhu, Baik Lin Seong, Kyoung Tai No, Hualiang Jiang, Hong Liu

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

With the introduction of bioisosteres of the guanidinium group together with scaffold hopping, 35 zanamivir analogs with C-4-modification were synthesized, and their inhibitory activities against both group-1 and group-2 neuraminidase (H5N1 and H3N2) were determined. Compound D26 exerts the most potency, with IC50 values of 0.58 and 2.72 μM against N2 and N1, respectively. Further preliminary anti-avian influenza virus (AIV, H5N1) activities against infected MDCK cells were evaluated, and D5 exerts ∼58% protective against AIV infection, which was comparable to zanamivir (∼67%). In a rat pharmacokinetic study, compound D5 showed an increased plasma half-life (t1/2) compared to zanamivir following either intravenous or oral administration. This study may represent a new start point for the future development of improved anti-AIV agents.

Original languageEnglish
Pages (from-to)764-770
Number of pages7
JournalEuropean Journal of Medicinal Chemistry
Volume54
DOIs
Publication statusPublished - 2012 Aug 1

Fingerprint

Zanamivir
Neuraminidase
Madin Darby Canine Kidney Cells
Pharmacokinetics
Influenza in Birds
Guanidine
Orthomyxoviridae
Viruses
Scaffolds
Intravenous Administration
Inhibitory Concentration 50
Oral Administration
Half-Life
Rats
Plasmas
Infection

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

Cite this

Ye, Deju ; Shin, Woo Jin ; Li, Ning ; Tang, Wei ; Feng, Enguang ; Li, Jian ; He, Pei Lan ; Zuo, Jian Ping ; Kim, Hanjo ; Nam, Ky Youb ; Zhu, Weiliang ; Seong, Baik Lin ; No, Kyoung Tai ; Jiang, Hualiang ; Liu, Hong. / Synthesis of C-4-modified zanamivir analogs as neuraminidase inhibitors and their anti-AIV activities. In: European Journal of Medicinal Chemistry. 2012 ; Vol. 54. pp. 764-770.
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Ye, D, Shin, WJ, Li, N, Tang, W, Feng, E, Li, J, He, PL, Zuo, JP, Kim, H, Nam, KY, Zhu, W, Seong, BL, No, KT, Jiang, H & Liu, H 2012, 'Synthesis of C-4-modified zanamivir analogs as neuraminidase inhibitors and their anti-AIV activities', European Journal of Medicinal Chemistry, vol. 54, pp. 764-770. https://doi.org/10.1016/j.ejmech.2012.06.033

Synthesis of C-4-modified zanamivir analogs as neuraminidase inhibitors and their anti-AIV activities. / Ye, Deju; Shin, Woo Jin; Li, Ning; Tang, Wei; Feng, Enguang; Li, Jian; He, Pei Lan; Zuo, Jian Ping; Kim, Hanjo; Nam, Ky Youb; Zhu, Weiliang; Seong, Baik Lin; No, Kyoung Tai; Jiang, Hualiang; Liu, Hong.

In: European Journal of Medicinal Chemistry, Vol. 54, 01.08.2012, p. 764-770.

Research output: Contribution to journalArticle

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AU - Ye, Deju

AU - Shin, Woo Jin

AU - Li, Ning

AU - Tang, Wei

AU - Feng, Enguang

AU - Li, Jian

AU - He, Pei Lan

AU - Zuo, Jian Ping

AU - Kim, Hanjo

AU - Nam, Ky Youb

AU - Zhu, Weiliang

AU - Seong, Baik Lin

AU - No, Kyoung Tai

AU - Jiang, Hualiang

AU - Liu, Hong

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