Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.7 (DNA polymerase)
 17,007 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The sugar boronated thymidine nucleoside, 5' -0-[(triphenylphosphine-boryl) carbonyl]-3'-0-acetyl thymidine 1, and the boron-modified nucleoside phosphotriester, 5'-(diethylphosphite- cyanoborane)-3'-acetylthymidine 2, were successfully synthesized. Both compounds demonstrated differential activity when tested against eight cell lines, with significant cytotoxic activity against the growth of human Tmolt3 leukemia, colon adenocarcinoma, HeLa S3 uterine carcinoma, and osteosarcoma cells. In in vivo studies these agents were found to be active against the growth of Ehrlich ascites carcinoma at 8 mg/kg/day I.P. and to be marginally active against the growth of L1210 and Lewis lung cancers in mice. The mode of action of these thymidine derivatives in Tmolt3 cells was the inhibition of DNA and protein synthesis. Compound 2 was highly effective in inhibiting DNA polymerase alpha and m-RNA, r-RNA and t-RNA polymerase activities. Both compounds inhibited ribonucleoside reductase activity. The de novo purine pathway appeared to be the major site of inhibition of the agents, with IMP dehydrogenase, PRPP amido transferase, and dihydrofolate reductase activities being significantly inhibited. In the pyrimidine pathway, carbamyl phosphate synthetase and aspartate transcarbamylase activities were inhibited by 1. As expected, d[NTP] levels were significantly reduced by treatment with the agents. DNA strand scission was evident after incubating Tmolt3 cells for 24 hr with the agents.
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PMID:Antineoplastic activity of boron-containing thymidine nucleosides in Tmolt3 leukemic cells. 150 1

Adenosine 5'[N,N-di-(gamma-o-carboranyl)propyl] phosphorodiamidate 1 was successfully synthesized and characterized. The compound demonstrated potent in vivo antineoplastic activity and in vitro cytotoxicity in murine and human leukemia and uterine carcinoma tumor cell lines. In human T cell leukemia DNA preferentially was inhibited with key enzymes in the purine pathway being effectively inhibited by the agent. Marginal inhibition of the activities DNA polymerase a, carbamyl phosphate synthetase, nucleoside kinases, and thymidylate synthetase was observed. Tmolt3 DNA strand scission was observed after 24 hr. incubation with compound I at 100 microM.
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PMID:The cytotoxicity of adenosine 5'-[N,N-di-(gamma-o-carboranyl)propyl] phosphorodiamidate in human Tmolt3 leukemic cells. 906 45