Cytotoxicity of a new IMP dehydrogenase inhibitor, benzamide riboside, to human myelogenous leukemia K562 cells

Hiremagalur N. Jayaram, Kamran Gharehbaghi, Nagesh H. Jayaram, Jason Rieser, Karsten Krohn, Kenneth D. Paull

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

COMPARE computer program suggested that benzamide riboside, BR, 3-(1-deoxy-β-D-ribofuranosyl)benzamide, should have a similar mechanism of action as that of tiazofurin, an inhibitor of IMP dehydrogenase (IMPDH). This hypothesis was tested in K562 cells in culture. BR was cytotoxic to K562 cells with an IC50 of 2 μM. Incubation of K562 cells with BR resulted in a significant decrease in GMP and GTP levels with a concurrent increase in IMP pools, and with a significant inhibition of IMPDH activity. However, 290-fold higher BR concentration was needed to demonstrate in vitro inhibition of IMPDH activity, suggesting that the agent may require metabolism to exert its action. These results provide evidence that BR is a new inhibitor of IMPDH. This investigation should be helpful to design new analogues having activity against IMPDH.

Original languageEnglish (US)
Pages (from-to)1600-1606
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume186
Issue number3
DOIs
StatePublished - Aug 14 1992

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IMP Dehydrogenase
Myeloid Leukemia
K562 Cells
Cytotoxicity
tiazofurin
Inosine Monophosphate
Guanosine Triphosphate
Metabolism
Inhibitory Concentration 50
Computer program listings
Software
Cell Culture Techniques
3-(1-deoxyribofuranosyl)benzamide

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Cytotoxicity of a new IMP dehydrogenase inhibitor, benzamide riboside, to human myelogenous leukemia K562 cells. / Jayaram, Hiremagalur N.; Gharehbaghi, Kamran; Jayaram, Nagesh H.; Rieser, Jason; Krohn, Karsten; Paull, Kenneth D.

In: Biochemical and Biophysical Research Communications, Vol. 186, No. 3, 14.08.1992, p. 1600-1606.

Research output: Contribution to journalArticle

Jayaram, Hiremagalur N. ; Gharehbaghi, Kamran ; Jayaram, Nagesh H. ; Rieser, Jason ; Krohn, Karsten ; Paull, Kenneth D. / Cytotoxicity of a new IMP dehydrogenase inhibitor, benzamide riboside, to human myelogenous leukemia K562 cells. In: Biochemical and Biophysical Research Communications. 1992 ; Vol. 186, No. 3. pp. 1600-1606.
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