Synthesis and Cytotoxic and Antiviral Profiling of Pyrrolo- and Furo-Fused 7-Deazapurine Ribonucleosides
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
- MeSH
- antivirové látky chemická syntéza chemie farmakologie MeSH
- furany chemie MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- protinádorové látky chemická syntéza chemie farmakologie MeSH
- puriny chemie MeSH
- pyrroly chemie MeSH
- ribonukleosidy chemická syntéza chemie farmakologie MeSH
- techniky syntetické chemie MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- 7-deazapurine MeSH Prohlížeč
- antivirové látky MeSH
- furan MeSH Prohlížeč
- furany MeSH
- protinádorové látky MeSH
- puriny MeSH
- pyrroly MeSH
- ribonukleosidy 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.
Citace poskytuje Crossref.org
Synthesis and Biological Profiling of Quinolino-Fused 7-Deazapurine Nucleosides
