Antipoliovirus structure-activity relationships of some aporphine alkaloids

J Nat Prod. 1998 Apr;61(4):480-4. doi: 10.1021/np970382v.

Abstract

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).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / chemistry*
  • Alkaloids / pharmacology*
  • Animals
  • Antiviral Agents / chemistry*
  • Antiviral Agents / pharmacology*
  • Aporphines / chemistry*
  • Aporphines / pharmacology*
  • Chlorocebus aethiops
  • Cytopathogenic Effect, Viral / drug effects
  • Herpesvirus 1, Human / drug effects
  • Humans
  • Models, Molecular
  • Poliovirus / drug effects*
  • Structure-Activity Relationship
  • Vero Cells
  • Virus Replication / drug effects

Substances

  • Alkaloids
  • Antiviral Agents
  • Aporphines