Antipoliovirus structure-activity relationships of some aporphine alkaloids.
A series of 18 aporphinoids have been tested in vitro against human poliovirus. The aporphines (+)-glaucine fumarate (1), (+)-N-methyllaurotetanine (4), (+)-isoboldine (7), and (-)-nuciferine, HCl (10) were found to be active with selectivity indices > 14. The nature of the 1, 2-substituents of the isoquinoline moiety appeared to be critical for antipoliovirus activity. An SAR study demonstrated the importance of a methoxyl group at C-2 on the tetrahydroisoquinoline ring for the induction of antipoliovirus activity. Molecular modeling of some compounds in this series revealed the close similarities between the three-dimensional conformational features of the inactive 1,2-substituted derivatives (+)-boldine (6) and (+)-laurolitsine (5) with derivatives containing the 1,2-(methylenedioxy) moiety, which were generally found to be inactive as exemplified by (+)-cassythicine (9).
Boustie
J
J
Laboratoire de Pharmacognosie et Mycologie, Faculté de Pharmacie, Université de Rennes, France.
Stigliani
J L
JL
Montanha
J
J
Amoros
M
M
Payard
M
M
Girre
L
L
D000470:Alkaloids / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D001060:Aporphines / Q000737:chemistry* / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D018259:Herpesvirus 1, Human / Q000187:drug effects; D006801:Humans; D008958:Models, Molecular; D017955:Poliovirus / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects
D000470:Alkaloids; D000998:Antiviral Agents; D001060:Aporphines