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Synthesis and Significant Cytostatic Activity of 7-Hetaryl-7-deazaadenosines

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, ORCID}
Number of authors	16
Source Title	Journal of Medicinal Chemistry. - : American Chemical Society - ISSN 0022-2623 Roč. 54, č. 15 (2011), s. 5498-5507
Number 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 ; Viktorie Chládková, Tel.: 232 002 434
Year of Publishing	2012

Number of the records: 1