Synthesis and Cytotoxic and Antiviral Profiling of Pyrrolo- and Furo-Fused 7-Deazapurine Ribonucleosides
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Antiviral Agents chemical synthesis chemistry pharmacology MeSH
- Furans chemistry MeSH
- Humans MeSH
- Cell Line, Tumor MeSH
- Antineoplastic Agents chemical synthesis chemistry pharmacology MeSH
- Purines chemistry MeSH
- Pyrroles chemistry MeSH
- Ribonucleosides chemical synthesis chemistry pharmacology MeSH
- Chemistry Techniques, Synthetic MeSH
- Structure-Activity Relationship MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- 7-deazapurine MeSH Browser
- Antiviral Agents MeSH
- furan MeSH Browser
- Furans MeSH
- Antineoplastic Agents MeSH
- Purines MeSH
- Pyrroles MeSH
- Ribonucleosides MeSH
Three series of isomeric pyrrolo- and furo-fused 7-deazapurine ribonucleosides were synthesized and screened for cytostatic and antiviral activity. The synthesis was based on heterocyclizations of hetaryl-azidopyrimidines to form the tricyclic heterocyclic bases, followed by glycosylation and final derivatizations through cross-coupling reactions or nucleophilic substitutions. The pyrrolo[2',3':4,5]pyrrolo[2,3- d]pyrimidine and furo[2',3':4,5]pyrrolo[2,3- d]pyrimidine ribonucleosides were found to be potent cytostatics, whereas the isomeric pyrrolo[3',2',4,5]pyrrolo[2,3- d]pyrimidine nucleosides were inactive. The most active were the methyl, methoxy, and methylsulfanyl derivatives exerting submicromolar cytostatic effects and good selectivity toward cancer cells. We have shown that the nucleosides are activated by intracellular phosphorylation and the nucleotides get incorporated to both RNA and DNA, where they cause DNA damage. They represent a new type of promising candidates for preclinical development toward antitumor agents.
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Synthesis and Biological Profiling of Quinolino-Fused 7-Deazapurine Nucleosides
