Anti-influenza virus activity and structure-activity relationship of aglycoristocetin derivatives with cyclobutenedione carrying hydrophobic chains

作者：Naesens Lieve^*; Vanderlinden Evelien; Roth Erzsebet; Jeko Jozsef; Andrei Graciela; Snoeck Robert; Pannecouque Christophe; Illyes Eszter; Batta Gyula; Herczegh Pal; Sztaricskai Ferenc

来源：Antiviral Research, 2009, 82(1): 89-94.

DOI：10.1016/j.antiviral.2009.01.003

• Glycopeptide antibiotic
• Ristocetin
• Influenza
• Antiviral

Previous studies have demonstrated that glycopeptide compounds carrying hydrophobic substituents can have favorable pharmacological (i.e. antibacterial and antiviral) properties. We here report on the in vitro anti-influenza virus activity of aglycoristocetin derivatives containing hydrophobic side chain-substituted cyclobutenedione. The lead compound 8e displayed an antivirally effective concentration of 0.4 mu M, which was consistent amongst influenza A/H1N1, A/H3N2 and B viruses, and a selectivity index >= 50. Structural analogues derived from aglycovancomycin were found to be inactive. The hydrophobic side chain was shown to be an important determinant of activity. The narrow structure-activity relationship and broad activity against several human influenza viruses suggest a highly conserved interaction site, which is presumably related to the influenza virus entry process. Compound 8e proved to be inactive against several unrelated RNA and DNA viruses, except for varicella-zoster virus, against which a favorable activity was noted.

• 出版日期2009-4
• 单位河北医科大学