Dinucleotide analogues as inhibitors of thymidine kinase, thymidylate kinase, and ribonucleotide reductase.
J Med Chem
; 31(7): 1305-8, 1988 Jul.
Article
em En
| MEDLINE
| ID: mdl-2838631
ABSTRACT
P1-(Adenosine-5')-Pn-(thymidine-5') tri-, tetra-, penta-, and hexaphosphates (ApnT) plus the analogues with a methylene group alpha, beta to the thymidine residue (ApncpT) were synthesized by coupling the appropriate two nucleotides, having activated one by morpholine. These were tested as potential dinucleotide inhibitors of thymidine kinase, thymidylate kinase, and ribonucleotide reductase. All three enzymes bind ATP and thymidine or its nucleotides and therefore might be inhibited by dinucleotides containing adenosine and thymidine. Ap5T and Ap6T strongly inhibited all three enzymes (IC50 = 2.4-20 microM). Ap4cpT and Ap5cpT also strongly inhibited the two kinases (IC50 = 4-20 microM) but were much weaker inhibitors of the reductase (IC50 = 130 and 230 microM).
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Base de dados:
MEDLINE
Assunto principal:
Oligonucleotídeos
/
Fosfotransferases
/
Ribonucleotídeo Redutases
/
Timidina Quinase
/
Núcleosídeo-Fosfato Quinase
Limite:
Animals
Idioma:
En
Ano de publicação:
1988
Tipo de documento:
Article