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- Title
Synthesis and Cytotoxic and Antiviral Activity Profiling of All‐Four Isomeric Series of Pyrido‐Fused 7‐Deazapurine Ribonucleosides.
- Authors
Veselovská, Lucia; Kudlová, Natálie; Gurská, Soňa; Lišková, Barbora; Medvedíková, Martina; Hodek, Ondřej; Tloušťová, Eva; Milisavljevic, Nemanja; Tichý, Michal; Perlíková, Pavla; Mertlíková‐Kaiserová, Helena; Trylčová, Jana; Pohl, Radek; Klepetářová, Blanka; Džubák, Petr; Hajdúch, Marián; Hocek, Michal
- Abstract
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.
- Subjects
RIBONUCLEOSIDES; PYRIMIDINE nucleosides; ANTINEOPLASTIC antibiotics; NUCLEOPHILIC substitution reactions
- Publication
Chemistry - A European Journal, 2020, Vol 26, Issue 57, p13002
- ISSN
0947-6539
- Publication type
Academic Journal
- DOI
10.1002/chem.202001124