Main structural and stereochemical aspects of the antiherpetic activity of nonahydroxyterphenoyl-containing C-glycosidic ellagitannins.
Antiherpetic evaluation of five nonahydroxyterphenoyl-containing C-glycosidic ellagitannins, castalagin (1), vescalagin (2), grandinin (3), roburin B (5), and roburin D (7), was performed in cultured cells against four HSV-1 and HSV-2 strains, two of which were resistant to Acyclovir. All five ellagitannins displayed significant anti-HSV activities against the Acyclovir-resistant mutants, but the monomeric structures 1-3 were more active than the dimers 5 and 7. Vescalagin (2) stands out among the five congeners tested as the most potent and selective inhibitor, with an IC50 value in the subfemtomolar range and a selectivity index 5x10(5) times higher than that of Acyclovir. Molecular modeling was used to provide a rationale for the surprisingly lower activity profile of its epimer castalagin (1). These ellagitannins have promising potential as novel inhibitors in the search for non-nucleoside drugs active against Acyclovir-resistant herpes viruses.
Quideau
Stéphane
S
Institut Européen de Chimie et Biologie, Pôle Chimie Organique et Bio-organique, 2 rue Robert Escarpit, F-33607 Pessac. s.quideau@iecb.u-bordeaux.fr
Varadinova
Tatiana
T
Karagiozova
Diana
D
Jourdes
Michael
M
Pardon
Patrick
P
Baudry
Christian
C
Genova
Petia
P
Diakov
Theodore
T
Petrova
Rozalina
R
D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology; D002417:Cattle; D002460:Cell Line; D006027:Glycosides / Q000737:chemistry* / Q000494:pharmacology; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000502:physiology; D018258:Herpesvirus 2, Human / Q000187:drug effects* / Q000502:physiology; D047348:Hydrolyzable Tannins / Q000737:chemistry* / Q000494:pharmacology; D013237:Stereoisomerism
D000998:Antiviral Agents; D006027:Glycosides; D047348:Hydrolyzable Tannins