Number of the records: 1

Phosphoramidate pronucleotides of cytostatic 6-aryl-7-deazapurine ribonucleosides

SYSNO ASEP	0360990
Document Type	J - Journal Article
R&D Document Type	Journal Article
Subsidiary J	Článek ve WOS
Title	Phosphoramidate pronucleotides of cytostatic 6-aryl-7-deazapurine ribonucleosides
Author(s)	Perlíková, Pavla (UOCHB-X)_{RID, ORCID} Pohl, Radek (UOCHB-X)_{RID, ORCID} Votruba, Ivan (UOCHB-X)_RID Shih, R. (US) Birkuš, G. (US) Cihlář, T. (US) Hocek, Michal (UOCHB-X)_{RID, ORCID}
Number of authors	7
Source Title	Bioorganic & Medicinal Chemistry. - : Elsevier - ISSN 0968-0896 Roč. 19, č. 1 (2011), s. 229-242
Number of pages	14 s.
Language	eng - English
Country	GB - United Kingdom
Keywords	nucleosides ; prodrugs ; proTides ; phosphoramidates ; pyrrolo[2,3-d]pyrimidines
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	000285724800022
DOI	10.1016/j.bmc.2010.11.029
Annotation	A series of O-phenyl methyl-, ethyl- and benzylalanyl phosphoramidate pronucleotides derived from cytostatic 6-aryl-7-deazapurine ribonucleosides were prepared by the cross-coupling reactions of the 2',3'-isopropylidene protected 6-chloro-7-deazapurine ribonucleoside phosphoramidates with (het)arylboronic acids or -stannanes followed by deprotection. Most of the prepared prodrugs exerted in vitro cytostatic effects against both solid tumor and lymphoid cancer cells within low micromolar range of concentrations. These activities were in general weaker or comparable to the activities of the parent nucleosides. Additional testing of selected prodrugs suggests that the lack of activity improvement over parent nucleosides is not due to the lack of permeability or inefficient catabolism of alanyl-ester by intracellular hydrolases. However, active efflux of prodrugs may play a role in their weak cytotoxic activity.
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