Synthesis and anti-trypanosomal activity of 3'-fluororibonucleosides derived from 7-deazapurine nucleosides
Language English Country Great Britain, England Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
33741462
DOI
10.1016/j.bmcl.2021.127957
PII: S0960-894X(21)00183-9
Knihovny.cz E-resources
- Keywords
- Anti-trypanosomal agents, Antiparasitic, Deazapurines, Fluorinated compounds, Nucleosides,
- MeSH
- Fibroblasts drug effects MeSH
- Humans MeSH
- Molecular Structure MeSH
- Cell Line, Tumor MeSH
- Parasitic Sensitivity Tests MeSH
- Ribonucleosides chemical synthesis pharmacology toxicity MeSH
- Trypanocidal Agents chemical synthesis pharmacology toxicity MeSH
- Trypanosoma brucei brucei drug effects MeSH
- Trypanosoma brucei gambiense drug effects MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Ribonucleosides MeSH
- Trypanocidal Agents 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.
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