Inactivation of S-adenosyl-L-homocysteine hydrolase by 6'-cyano-5',6'-didehydro-6'-deoxyhomoadenosine and 6'-chloro-6'-cyano-5',6'-didehydro-6'-deoxyhomoadenosine. Antiviral and cytotoxic effects

J Med Chem. 2006 Feb 23;49(4):1223-6. doi: 10.1021/jm051023x.

Abstract

6'-Cyano-5',6'-didehydro-6'-deoxyhomoadenosine (E)-1, (Z)-1, and 6'-chloro-6'-cyano-5',6'-didehydro-6'-deoxyhomoadenosine (E)-2 were synthesized and tested as new mechanism-based inhibitors of AdoHcy hydrolase. Nucleoside (E)-1 was identified as a type I inhibitor of the enzyme, whereas inactivation of the enzyme by nucleosides (Z)-1 and (E)-2 was accompanied by the formation of a covalent labeling of AdoHcy hydrolase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosylhomocysteinase / antagonists & inhibitors*
  • Adenosylhomocysteinase / chemistry
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology
  • Cells, Cultured
  • Cytomegalovirus / drug effects
  • Deoxyadenosines / chemical synthesis*
  • Deoxyadenosines / chemistry
  • Deoxyadenosines / pharmacology
  • Herpesvirus 3, Human / drug effects
  • Humans
  • Nucleosides / chemical synthesis*
  • Nucleosides / chemistry
  • Nucleosides / pharmacology
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • 6'-chloro-6'-cyano-5',6'-didehydro-6'-deoxyhomoadenosine
  • 6'-cyano-5',6'-didehydro-6'-deoxyhomoadenosine
  • Antineoplastic Agents
  • Antiviral Agents
  • Deoxyadenosines
  • Nucleosides
  • Adenosylhomocysteinase