Synthesis and Biological Evaluation of Some 4'-C-(Hydroxymethyl)-α- and -β-D-Arabinofuranosyl Pyrimidine and Adenine Nucleosides

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Title:Synthesis and Biological Evaluation of Some 4'-C-(Hydroxymethyl)-α- and -β-D-Arabinofuranosyl Pyrimidine and Adenine Nucleosides
Creators:
Griffon, Jean-François
Shaddix, Sue C.
Parker, William B.
Al-Madhoun, Ashraf S.
Eriksson, Staffan
Montgomery, John A.
Secrist III, John A.
Journal or Publication Title:
Collection of Czechoslovak Chemical Communications, 71, 7, pp. 1063-1087
Uncontrolled Keywords:Pyrimidines, 4'-<i>C</i>-Branched nucleosides, Purines, Phosphorylation, Glycosidation, Deoxycytidine kinase, Cytotoxicity, 4'-<i>C</i>-(Hydroxymethyl)nucleosides

Abstract

A series of 4'-<i>C</i>-(hydroxymethyl) analogs of pyrimidine and purine nucleosides have been prepared utilizing standard methodologies, and the α and β anomers were separated. These analogs are part of our continuing efforts to identify new anticancer drugs as well as to explore the substrate specificities of these analogs with the initial activating enzymes in the metabolic pathway leading to nucleoside triphosphates. Although not cytotoxic to CCRF-CEM cells (an acute lymphoblastic leukemia of T-cell origin), many of these compounds were utilized as substrates for the various human nucleoside kinases, including deoxycytidine kinase, thymidine kinase 1, and thymidine kinase 2. Because the 4'-<i>C</i>-(hydroxymethyl) analog of arabinofuranosyl cytosine was identified as a good substrate with deoxycytidine kinase, its metabolism in CEM cells was evaluated. These results indicated that nucleosides with this modification could be activated in human cells without cytotoxicity, which suggested that they should be examined for antiviral activity. <p>

Title:Synthesis and Biological Evaluation of Some 4'-C-(Hydroxymethyl)-α- and -β-D-Arabinofuranosyl Pyrimidine and Adenine Nucleosides
Creators:
Griffon, Jean-François
Shaddix, Sue C.
Parker, William B.
Al-Madhoun, Ashraf S.
Eriksson, Staffan
Montgomery, John A.
Secrist III, John A.
Uncontrolled Keywords:Pyrimidines, 4'-<i>C</i>-Branched nucleosides, Purines, Phosphorylation, Glycosidation, Deoxycytidine kinase, Cytotoxicity, 4'-<i>C</i>-(Hydroxymethyl)nucleosides
Divisions:Life and Chemical Sciences > Institute of Organic Chemistry and Biochemistry > Collection of Czechoslovak Chemical Communications
Journal or Publication Title:Collection of Czechoslovak Chemical Communications
Volume:71
Number:7
Page Range:pp. 1063-1087
ISSN:0010-0765
E-ISSN:1212-6950
Publisher:Institute of Organic Chemistry and Biochemistry
Related URLs:
URLURL Type
http://dx.doi.org/10.1135/cccc20061063UNSPECIFIED
ID Code:2525
Item Type:Article
Deposited On:06 Feb 2009 17:19
Last Modified:06 Feb 2009 16:19

Citation

Griffon, Jean-François; Shaddix, Sue C.; Parker, William B.; Al-Madhoun, Ashraf S.; Eriksson, Staffan; Montgomery, John A.; Secrist III, John A. (2006) Synthesis and Biological Evaluation of Some 4'-C-(Hydroxymethyl)-α- and -β-D-Arabinofuranosyl Pyrimidine and Adenine Nucleosides. Collection of Czechoslovak Chemical Communications, 71 (7). pp. 1063-1087. ISSN 0010-0765

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