Synthesis and anti-trypanosomal activity of 3'-fluororibonucleosides derived from 7-deazapurine nucleosides
Jazyk angličtina Země Velká Británie, Anglie Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
Odkazy
PubMed
33741462
DOI
10.1016/j.bmcl.2021.127957
PII: S0960-894X(21)00183-9
Knihovny.cz E-zdroje
- Klíčová slova
- Anti-trypanosomal agents, Antiparasitic, Deazapurines, Fluorinated compounds, Nucleosides,
- MeSH
- fibroblasty účinky léků MeSH
- lidé MeSH
- molekulární struktura MeSH
- nádorové buněčné linie MeSH
- parazitické testy citlivosti MeSH
- ribonukleosidy chemická syntéza farmakologie toxicita MeSH
- trypanocidální látky chemická syntéza farmakologie toxicita MeSH
- Trypanosoma brucei brucei účinky léků MeSH
- Trypanosoma brucei gambiense účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- ribonukleosidy MeSH
- trypanocidální látky MeSH
Trypanosoma brucei parasites cause Human African Trypanosomiasis and the current drugs for its treatment are often inefficient and toxic. This urges the need to development of new antitrypanosomal agents. We report the synthesis and biological profiling of 3'-deoxy-3'-fluororibonucleosides derived from 7-deazaadenine nucleosides bearing diverse substituents at position 7. They were synthesized through glycosylation of 6-chloro-7-bromo- or -7-iodo-7-deazapurine with protected 3'-fluororibose followed by cross-coupling reactions at position 7 and/or deprotection. Most of the title nucleosides displayed micromolar or submicromolar activity against Trypanosoma brucei brucei. The most active were the 7-bromo- and 7-iododerivatives which exerted double-digit nanomolar activity against T. b. brucei and T. b. gambiense and no cytotoxicity and thus represent promising candidates for further development.
