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Synthesis and Significant Cytostatic Activity of 7-Hetaryl-7-deazaadenosines
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SYSNO ASEP 0364270 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Synthesis and Significant Cytostatic Activity of 7-Hetaryl-7-deazaadenosines Author(s) Bourderioux, Aurelie (UOCHB-X)
Nauš, Petr (UOCHB-X) RID
Perlíková, Pavla (UOCHB-X) RID, ORCID
Pohl, Radek (UOCHB-X) RID, ORCID
Pichová, Iva (UOCHB-X) RID, ORCID
Votruba, Ivan (UOCHB-X) RID
Džubák, P. (CZ)
Konečný, P. (CZ)
Hajdúch, M. (CZ)
Stray, K. M. (US)
Wang, T. (US)
Ray, A. S. (US)
Feng, J. Y. (US)
Birkuš, G. (US)
Cihlar, T. (US)
Hocek, Michal (UOCHB-X) RID, ORCIDNumber of authors 16 Source Title Journal of Medicinal Chemistry. - : American Chemical Society - ISSN 0022-2623
Roč. 54, č. 15 (2011), s. 5498-5507Number of pages 10 s. Language eng - English Country US - United States Keywords adenosine-kinase-inhibitors ; cross-coupling reactions ; cytotoxic nucleoside analogs ; enzyme-inhibition ; ribonucleosides Subject RIV CC - Organic Chemistry R&D Projects 1M0508 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) GAP207/11/0344 GA ČR - Czech Science Foundation (CSF) CEZ AV0Z40550506 - UOCHB-X (2005-2011) UT WOS 000293419400021 DOI 10.1021/jm2005173 Annotation A series of 7-aryl- and 7-hetaryl-7-deazaadenosines were prepared by the cross-coupling reactions of unprotected or protected 7-iodo-7-deazaadenosines with (het)arylboronic acids, stannanes or zinc halides. Nucleosides bearing 5-membered heterocycles at the position 7 exerted potent in vitro anti-proliferative effects against a broad panel of hematological and solid tumor cell lines. Cell cycle analysis indicated profound inhibition of RNA synthesis and induction of apoptosis in treated cells. Intracellular conversion to triphosphates has been detected with active compounds. The triphosphate metabolites showed only a weak inhibitory effect on human RNA polymerase II, suggesting potentially other mechanisms for the inhibition of RNA synthesis and quick onset of apoptosis. Initial in vivo evaluation demonstrated an effect of 7-(2-thienyl)-7-deazaadenine ribonucleoside on the survival rate in syngeneic P388D1 mouse leukemia model. Workplace Institute of Organic Chemistry and Biochemistry Contact asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Jana Procházková, Tel.: 220 183 418 Year of Publishing 2012
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