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Antiviral Res. Anti-influenza virus activity and structure-activity relationship of aglycoristocetin derivatives with cyclobutenedione carrying hydrop

Giuseppe

Emeritus
Antiviral Res. 2009 Feb 4. [Epub ahead of print]

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

Naesens L, Vanderlinden E, Rőth E, Jekő J, Andrei G, Snoeck R, Pannecouque C, Illy?s E, Batta G, Herczegh P, Sztaricskai F. - Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium.

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 0.4muM, 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.

PMID: 19200809 [PubMed - as supplied by publisher]
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