Pharmacobiochemical properties of 5-alkyl-deoxyuridines. Effects of 5-hexyl-2'-deoxyuridine on tumor growth and glycoconjugate synthesis

A. Jeney, L. Kopper, E. Hidvegi, K. Lapis, A. Szabolcs, L. Otvos

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Abstract

The antiproliferative and DNA synthesis inhibitory activities of 5-alkyl substituted deoxyuridines were investigated. The lengthening of the alkyl group showed that 5-hexyl-2'-deoxyuridine (HUdR) had the strongest antitumor activity on Ehrlich ascites tumor bearing mice. A similar conclusion was drawn upon studying the relationship between the chemical structure of deoxyuridines and the incorporation of 3H-thymidine into DNA. However, the reduction of 3H-thymidine incorporation into DNA did not appear to exert a direct effect on nucleotide metabolism. The lack of any indication of thymidylate synthetase inhibition and of the incorporation of (2-14C)-HUdR into nucleic acid, is probably due to the fact that HUdR was not a substrate of the phosphorylation reaction. At the same time (2-14C)-HUdR showed a preferential association to Golgi apparatus and plasma membranes. In addition, a remarkable reduction was observed in the rate of incorporation of radioactive glucosamines into various glycoconjugate fractions, especially into glycosaminoglycans of HUdR treated cells.

Original languageEnglish
Pages (from-to)32-39
Number of pages8
JournalInternational Journal of Experimental and Clinical Chemotherapy
Volume4
Issue number1
Publication statusPublished - Jan 1 1991

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ASJC Scopus subject areas

  • Pharmacology

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