Synthesis and anti-trypanosomal activity of 3′-fluororibonucleosides derived from 7-deazapurine nucleosides

0541603 - ÚOCHB 2022 RIV GB eng J - Journal Article
Nguyen, Van Hai - Tichý, Michal - Rožánková, Samanta - Pohl, Radek - Downey, Alan Michael - Doleželová, Eva - Tloušťová, Eva - Slapničková, Martina - Zíková, Alena - Hocek, Michal
Synthesis and anti-trypanosomal activity of 3′-fluororibonucleosides derived from 7-deazapurine nucleosides.
Bioorganic and Medicinal Chemistry Letters. Roč. 40, May 15 (2021), č. článku 127957. ISSN 0960-894X. E-ISSN 1464-3405
R&D Projects: GA ČR(CZ) GA19-08124S; GA ČR(CZ) GA19-07707S
Grant - others:AV ČR(CZ) AP1501
Program: Akademická prémie - Praemium Academiae
Institutional support: RVO:61388963 ; RVO:60077344
Keywords : nucleosides * deazapurines * fluorinated compounds * antiparasitic * anti-trypanosomal agents
OECD category: Organic chemistry; Organic chemistry (BC-A)
Impact factor: 2.940, year: 2021
Method of publishing: Limited access
https://doi.org/10.1016/j.bmcl.2021.127957

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.
Permanent Link: http://hdl.handle.net/11104/0319136