5-azacytosine compounds in medicinal chemistry: current stage and future perspectives.

Abstract

This review summarizes the basic milestones of the research of 5-azacytosine nucleosides chronologically from their discovery and anticancer activity identification, through to subsequent unveiling of their mechanism of action based on DNA hypomethylation and tumor-suppressor gene reactivation, to the final US FDA approval of 5-azacytidine (Vidaza(®)) and 2'-deoxy-5-azacytidine (Dacogen(®)) for the treatment of myelodysplastic syndromes. 5,6-dihydro-2'-deoxy-5-azacytidine, a compound with anti-HIV activity through lethal mutagenesis, representing a unique mechanism of action among existing anti-retroviral drugs, is discussed together with quite recent discovery of its so far unexpected hypomethylation activity. Special attention is paid to 5-azacytosine acyclic nucleoside analogues and phosphonomethyl derivatives with the emphasis on the new potent anti-DNA virus agent (S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]-5-azacytosine and its prodrug forms. Considering the potential pharmaceutical applications, 5-azacytosine and 5,6-dihydro-5-azacytosine appear to be so far the most effective cytosine mimics for the design of novel antiviral and anti-tumor drug candidates.

• Authors: Marcela Krečmerová, Miroslav Otmar
• Journal: Future medicinal chemistry (Future Med Chem) Vol. 4 Issue 8 Pg. 991-1005 (May 2012) ISSN: 1756-8927 [Electronic] England
• PMID: 22650240 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Anti-HIV Agents
• Antineoplastic Agents
• 5,6-dihydro-5-azacytidine
• 5-azacytosine
• Cytosine
• Azacitidine

Topics

• Animals
• Anti-HIV Agents (chemistry, pharmacology, therapeutic use)
• Antineoplastic Agents (chemistry, pharmacology, therapeutic use)
• Azacitidine (analogs & derivatives, chemistry, pharmacology, therapeutic use)
• Cytosine (analogs & derivatives, chemistry, pharmacology, therapeutic use)
• DNA Methylation (drug effects)
• Drug Discovery
• HIV (drug effects)
• HIV Infections (drug therapy)
• Humans
• Neoplasms (drug therapy)