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

Abstract：

:COMPARE computer program suggested that benzamide riboside, BR, 3-(1-deoxy-beta-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 microM. 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.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Jayaram HN,Gharehbaghi K,Jayaram NH,Rieser J,Krohn K,Paull KD

doi

10.1016/s0006-291x(05)81591-8

subject

Has Abstract

pub_date

1992-08-14 00:00:00

pages

1600-6

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(05)81591-8

journal_volume

186

pub_type

杂志文章

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