2',3'-didehydro-2',3'-dideoxy-5-chlorocytidine is a selective anti-retrovirus agent.

Abstract

2',3'-Didehydro-2',3'-dideoxy-5-chlorocytidine (D4CC) is, in contrast with 2',3'-dideoxy-5-chlorocytidine (ddClCyd) and 2',3'-didehydro-2',3'-dideoxy-5-chlorouridine (D4CU), a potent and selective inhibitor of the replication of human immunodeficiency virus (HIV) types 1 and 2, simian immunodeficiency virus (SIV) and simian AIDS related virus (SRV). D4CC is a poor inhibitor of the phosphorylation of [5-3H]2'-deoxycytidine (dCyd) by partially purified MT-4 cell dCyd kinase (Ki: 612 microM). The findings that (i) D4CC has little, if any, affinity for MT-4 cell Cyd/dCyd deaminase, (ii) D4CU is not antivirally active and (iii) the antiretroviral action of D4CC can be reversed by dCyd, but not dThd, indicate that D4CC is antivirally active as its Cyd metabolite (D4CC 5'-triphosphate) and does not need to be deaminated (to the corresponding Urd metabolite) to exert its antiretroviral action.

• Authors: J Balzarini, A Van Aerschot, P Herdewijn, E De Clercq
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 164 Issue 3 Pg. 1190-7 (Nov 15 1989) ISSN: 0006-291X [Print] United States
• PMID: 2590197 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• Deoxycytidine
• 2',3'-didehydro-2',3'-dideoxy-5-chlorocytidine
• Deoxycytidine Kinase
• Cytidine Deaminase

Topics

• Antiviral Agents (pharmacology)
• Cell Line
• Cytidine Deaminase (antagonists & inhibitors)
• Deoxycytidine (pharmacology)
• Deoxycytidine Kinase (antagonists & inhibitors)
• HIV-1 (drug effects)
• HIV-2 (drug effects)
• Humans
• Molecular Structure
• Retroviridae (drug effects)
• Simian Immunodeficiency Virus (drug effects)
• Structure-Activity Relationship