Enhanced Anti-influenza Agents Conjugated with Anti-inflammatory Activity
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- 作者：Kung-Cheng Liu ; Jim-Min Fang ; Jia-Tsrong Jan ; Ting-Jen R. Cheng ; Shi-Yun Wang ; Shi-Ting Yang ; Yih-Shyun E. Cheng ; Chi-Huey Wong
- 刊名：Journal of Medicinal Chemistry
- 出版年：2012
- 出版时间：October 11, 2012
- 年：2012
- 卷：55
- 期：19
- 页码：8493-8501
- 全文大小：521K
- 年卷期：v.55,no.19(October 11, 2012)
- ISSN：1520-4804
文摘
Influenza therapy with a single targeted compound is often limited in efficacy due to the rapidly developed drug resistance. Moreover, the uncontrolled virus-induced cytokines could cause the high mortality of human infected by H5N1 avian influenza virus. In this study, we explored the novel dual-targeted bifunctional anti-influenza drugs formed by conjugation with anti-inflammatory agents. In particular, the caffeic acid (CA)-bearing zanamivir (ZA) conjugates ZA-7-CA (1) and ZA-7-CA-amide (7) showed simultaneous inhibition of influenza virus neuraminidase and suppression of pro-inflammatory cytokines. These ZA conjugates provided remarkable protection of cells and mice against influenza infections. Intranasal administration of low dosage (<1.2 渭mol/kg/day) of ZA conjugates exhibited much greater effect than the combination therapy with ZA and the anti-inflammatory agents in protection of the lethally infected mice by H1N1 or H5N1 influenza viruses.