title: Anti-influenza virus activity and structure-activity relationship of aglycoristocetin derivatives with cyclobutenedione carrying hydrophobic chains.
abstract: 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 microM, which was consistent amongst influenza A/H1N1, A/H3N2 and B viruses, and a selectivity index > or =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.
authors.affiliation: Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium. lieve.naesens@rega.kuleuven.be
authors.forename: Lieve
authors.initials: L
authors.lastname: Naesens
authors.forename: Evelien
authors.initials: E
authors.lastname: Vanderlinden
authors.forename: Erzsébet
authors.initials: E
authors.lastname: Roth
authors.forename: József
authors.initials: J
authors.lastname: Jeko
authors.forename: Graciela
authors.initials: G
authors.lastname: Andrei
authors.forename: Robert
authors.initials: R
authors.lastname: Snoeck
authors.forename: Christophe
authors.initials: C
authors.lastname: Pannecouque
authors.forename: Eszter
authors.initials: E
authors.lastname: Illyés
authors.forename: Gyula
authors.initials: G
authors.lastname: Batta
authors.forename: Pál
authors.initials: P
authors.lastname: Herczegh
authors.forename: Ferenc
authors.initials: F
authors.lastname: Sztaricskai
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D006020:Glycopeptides / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007251:Influenza, Human / Q000188:drug therapy / Q000821:virology; D009975:Orthomyxoviridae / Q000187:drug effects* / Q000502:physiology; D013329:Structure-Activity Relationship
chemical_list: D000998:Antiviral Agents; D006020:Glycopeptides