Synthesis and Cytotoxic and Antiviral Activity Profiling of All‐Four Isomeric Series of Pyrido‐Fused 7‐Deazapurine Ribonucleosides
| العنوان: | Synthesis and Cytotoxic and Antiviral Activity Profiling of All‐Four Isomeric Series of Pyrido‐Fused 7‐Deazapurine Ribonucleosides |
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| المؤلفون: | Pavla Perlíková, Marian Hajduch, Blanka Klepetářová, Martina Medvedíková, Nemanja Milisavljevic, Helena Mertlíková-Kaiserová, Petr Džubák, Barbora Lišková, Jana Trylčová, Eva Tloušťová, Radek Pohl, Michal Tichý, Michal Hocek, Ondřej Hodek, Lucia Veselovská, Soňa Gurská, Natálie Kudlová |
| المصدر: | Chemistry – A European Journal. 26:13002-13015 |
| بيانات النشر: | Wiley, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Glycosylation, Pyrimidine, 010405 organic chemistry, Stereochemistry, Organic Chemistry, Total synthesis, Antineoplastic Agents, General Chemistry, 010402 general chemistry, Antiviral Agents, 01 natural sciences, Catalysis, 0104 chemical sciences, Structure-Activity Relationship, chemistry.chemical_compound, chemistry, Nucleophile, Purines, Pyridine, Ribonucleosides, Derivatization, Selectivity, DNA |
| الوصف: | 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. |
| تدمد: | 1521-3765 0947-6539 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fc07fdfb9d5d82341afc0bcd299b3771 https://doi.org/10.1002/chem.202001124 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....fc07fdfb9d5d82341afc0bcd299b3771 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15213765 09476539 |
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