(D)- and (L)-cyclohexenyl-G, a new class of antiviral agents: synthesis, conformational analysis, molecular modeling, and biological activity

Nucleosides Nucleotides Nucleic Acids. 2001 Apr-Jul;20(4-7):727-30. doi: 10.1081/NCN-100002360.

Abstract

(D)- and (L)-cyclohexeneyl-G were synthesized enantioselectively starting from (R)-carvone. Both show potent and selective anti-herpesvirus activity (HSV-1, HSV-2, VZV, CMV). Molecular modeling demonstrates that both isomers are bound in the active site of HSV-1 thymidine kinase in a high-energy conformation with the base moiety orienting in an equatorial position. It is believed that the flexibility of the cyclohexene ring is essential for their antiviral activity.

MeSH terms

  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry*
  • Antiviral Agents / pharmacology*
  • Cyclohexane Monoterpenes
  • Cyclohexanes / chemical synthesis
  • Cyclohexanes / chemistry*
  • Cyclohexanes / pharmacology
  • Cyclohexenes
  • Guanine / analogs & derivatives*
  • Guanine / chemical synthesis
  • Guanine / chemistry*
  • Guanine / pharmacology
  • Herpesviridae / drug effects
  • Herpesviridae / enzymology
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Molecular Conformation
  • Monoterpenes
  • Stereoisomerism
  • Terpenes / chemistry
  • Thymidine Kinase / metabolism

Substances

  • Antiviral Agents
  • Cyclohexane Monoterpenes
  • Cyclohexanes
  • Cyclohexenes
  • Monoterpenes
  • Terpenes
  • cyclohexenyl-G
  • cyclohexene
  • Guanine
  • carvone
  • Thymidine Kinase