Synthesis and Antitrypanosomal Activity of 6-Substituted 7-Methyl-7-deazapurine Nucleosides

0541879 - ÚOCHB 2022 RIV US eng J - Journal Article
Perlíková, Pavla - Krajczyk, Anna - Doleželová, Eva - Slapničková, Martina - Milisavljevič, Nemanja - Poštová Slavětínská, Lenka - Tloušťová, Eva - Gurská, S. - Džubák, P. - Hajdúch, M. - Zíková, Alena - Hocek, Michal
Synthesis and Antitrypanosomal Activity of 6-Substituted 7-Methyl-7-deazapurine Nucleosides.
ACS Infectious Diseases. Roč. 7, č. 4 (2021), s. 917-926. ISSN 2373-8227
R&D Projects: GA MŠMT(CZ) EF16_019/0000729; GA MŠMT(CZ) EF16_019/0000759; GA ČR(CZ) GA19-08124S; GA ČR(CZ) GA19-07707S; GA MŠMT(CZ) LM2015064
Grant - others:AV ČR(CZ) AP1501
Program: Akademická prémie - Praemium Academiae
Institutional support: RVO:61388963 ; RVO:60077344
Keywords : nucleosides * antiparasitic activity * antitrypanosomal * cytotoxicity
OECD category: Organic chemistry; Organic chemistry (BC-A)
Impact factor: 5.578, year: 2021
Method of publishing: Limited access
https://doi.org/10.1021/acsinfecdis.1c00062

Human African Trypanosomiasis caused by Trypanosoma brucei species is one of the most damaging neglected tropical diseases. While the number of newly diagnosed cases per year is record low, there is still high interest in the development of new antitrypanosomal agents in case of resistance to currently used drugs and their combinations, and to replace drugs with serious side effects. We report a series of 7-methyl-7-deazapurine (5-methyl-pyrrolo[2,3-d]pyrimidine) ribonucleosides bearing alkyl, methylsulfanyl, methylamino, or diverse alkoxy groups at position 6 that was prepared through glycosylation of 6-chloro-7-methyl-7-deazapurine followed by nucleophilic substitutions or cross-coupling reactions at position 6 and deprotection. Most of the title nucleosides displayed significant activity against Trypanosoma brucei brucei and T. b. gambiense at submicromolar or nanomolar concentrations and low cytotoxicity and thus represent promising candidates for further development.
Permanent Link: http://hdl.handle.net/11104/0319376