title: Synthesis and anti-influenza virus activities of a novel class of gastrodin derivatives.
abstract: A series of substituted aryl glycoside analogues of gastrodin have been identified as potential anti-influenza agents. The most potent inhibitor 1a exhibited moderate inhibitory activity against the A/Hanfang/359/95(H3N2) and A/FM/1/47(H1N1) strains of the influenza A virus (IC(50) values of 44.40 and 34.45 μM, respectively) and the oseltamivir-null B/Jifang/13/97 strain of influenza B (IC(50) value of 33.01 μM). In this article, multiple doses of compound 1a (80 mg/kg/day, oral administration) were used for the treatment of mice infected with influenza A/FM/1/47-MA (H1N1), and surprisingly we found that compound 1a significantly increased the number of survivors and prolonged the mean survival time. The preliminary studies on the mechanism of antiviral activity showed no interaction between compound 1a and the neuraminidase or the M2 protein. The novel target to overcome drug resistance combined with its good in vivo profile support compound 1a to be a new lead for further development of antiviral agents.
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
authors.forename: Si-Tu
authors.initials: ST
authors.lastname: Xue
authors.forename: Wei-Ying
authors.initials: WY
authors.lastname: He
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Ma
authors.forename: Hui-Qiang
authors.initials: HQ
authors.lastname: Wang
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.forename: Guang-Hui
authors.initials: GH
authors.lastname: Zheng
authors.forename: Xing-Yue
authors.initials: XY
authors.lastname: Ji
authors.forename: Tian
authors.initials: T
authors.lastname: Zhang
authors.forename: Yu-Huan
authors.initials: YH
authors.lastname: Li
authors.forename: Jian-Dong
authors.initials: JD
authors.lastname: Jiang
authors.forename: Zhuo-Rong
authors.initials: ZR
authors.lastname: Li
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001592:Benzyl Alcohols / Q000138:chemical synthesis* / Q000494:pharmacology; D005260:Female; D005960:Glucosides / Q000138:chemical synthesis* / Q000494:pharmacology; D006384:Hemagglutination / Q000187:drug effects; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000254:growth & development; D020128:Inhibitory Concentration 50; D051379:Mice; D009439:Neuraminidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D053139:Oseltamivir / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014763:Viral Matrix Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D000086082:Viroporin Proteins
chemical_list: D000998:Antiviral Agents; D001592:Benzyl Alcohols; D005960:Glucosides; D009439:Neuraminidase; D053139:Oseltamivir; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins; C045345:gastrodin