Synthesis and Cytotoxic and Antiviral Activity Profiling of All-Four Isomeric Series of Pyrido-Fused 7-Deazapurine Ribonucleosides

0532766 - ÚOCHB 2021 RIV DE eng J - Journal Article
Veselovská, Lucia - Kudlová, N. - Gurská, S. - Lišková, B. - Medvedíková, M. - Hodek, Ondřej - Tloušťová, Eva - Milisavljevič, Nemanja - Tichý, Michal - Perlíková, Pavla - Mertlíková-Kaiserová, Helena - Trylčová, Jana - Pohl, Radek - Klepetářová, Blanka - Džubák, P. - Hajdúch, M. - Hocek, Michal
Synthesis and Cytotoxic and Antiviral Activity Profiling of All-Four Isomeric Series of Pyrido-Fused 7-Deazapurine Ribonucleosides.
Chemistry - A European Journal. Roč. 26, č. 57 (2020), s. 13002-13015. ISSN 0947-6539. E-ISSN 1521-3765
R&D Projects: GA ČR(CZ) GA19-08124S; GA MZd(CZ) NV15-31984A; GA MŠMT(CZ) LM2015064
Grant - others:AV ČR(CZ) AP1501
Program: Akademická prémie - Praemium Academiae
Institutional support: RVO:61388963
Keywords : antitumor agents * antiviral agents * drug discovery * phosphorylation * ribonucleosides
OECD category: Organic chemistry
Impact factor: 5.236, year: 2020
Method of publishing: Limited access
https://doi.org/10.1002/chem.202001124

All four isomeric series of novel 4‐substituted pyrido‐fused 7‐deazapurine ribonucleosides possessing the pyridine nitrogen atom at different positions were designed and synthesized. The total synthesis of each isomeric fused heterocycle through multistep heterocyclization was followed by glycosylation and derivatization at position 4 by cross‐coupling reactions or nucleophilic substitutions. All compounds were tested for cytostatic and antiviral activity. The most active were pyrido[4′,3′:4,5]pyrimidine nucleosides bearing MeO, NH2, MeS, or CH3 groups at position 4, which showed submicromolar cytotoxic effects and good selectivity for cancer cells. The mechanism involved activation by phosphorylation and incorporation to DNA where the presence of the modified ribonucleosides causes double‐strand breaks and apoptosis.
Permanent Link: http://hdl.handle.net/11104/0311179