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Antineoplastic activity of boron-containing thymidine nucleosides in Tmolt3 leukemic cells.

Publication ,  Journal Article
Hall, IH; Hall, ES; Chi, LK; Shaw, BR; Sood, A; Spielvogel, BF
Published in: Anticancer research
July 1992

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.

Duke Scholars

Published In

Anticancer research

EISSN

1791-7530

ISSN

0250-7005

Publication Date

July 1992

Volume

12

Issue

4

Start / End Page

1091 / 1097

Related Subject Headings

  • Tumor Cells, Cultured
  • Thymine Nucleotides
  • Thymidine
  • Oncology & Carcinogenesis
  • Mice, Inbred DBA
  • Mice
  • Male
  • Leukemia, T-Cell
  • Leukemia P388
  • Leukemia L1210
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Hall, I. H., Hall, E. S., Chi, L. K., Shaw, B. R., Sood, A., & Spielvogel, B. F. (1992). Antineoplastic activity of boron-containing thymidine nucleosides in Tmolt3 leukemic cells. Anticancer Research, 12(4), 1091–1097.
Hall, I. H., E. S. Hall, L. K. Chi, B. R. Shaw, A. Sood, and B. F. Spielvogel. “Antineoplastic activity of boron-containing thymidine nucleosides in Tmolt3 leukemic cells.Anticancer Research 12, no. 4 (July 1992): 1091–97.
Hall IH, Hall ES, Chi LK, Shaw BR, Sood A, Spielvogel BF. Antineoplastic activity of boron-containing thymidine nucleosides in Tmolt3 leukemic cells. Anticancer research. 1992 Jul;12(4):1091–7.
Hall, I. H., et al. “Antineoplastic activity of boron-containing thymidine nucleosides in Tmolt3 leukemic cells.Anticancer Research, vol. 12, no. 4, July 1992, pp. 1091–97.
Hall IH, Hall ES, Chi LK, Shaw BR, Sood A, Spielvogel BF. Antineoplastic activity of boron-containing thymidine nucleosides in Tmolt3 leukemic cells. Anticancer research. 1992 Jul;12(4):1091–1097.

Published In

Anticancer research

EISSN

1791-7530

ISSN

0250-7005

Publication Date

July 1992

Volume

12

Issue

4

Start / End Page

1091 / 1097

Related Subject Headings

  • Tumor Cells, Cultured
  • Thymine Nucleotides
  • Thymidine
  • Oncology & Carcinogenesis
  • Mice, Inbred DBA
  • Mice
  • Male
  • Leukemia, T-Cell
  • Leukemia P388
  • Leukemia L1210