POTENTIATION OF 2'-DEOXYGUANOSINE CYTOTOXICITY BY A NOVEL INHIBITOR OF PURINE NUCLEOSIDE PHOSPHORYLASE, 8-AMINO-9-BENZYLGUANINE
- 1 February 1986
- journal article
- research article
- Vol. 46 (2) , 519-523
Abstract
We have synthesized and evaluated a series of 9-substituted analogues of 8-aminoguanine, a known inhibitor of human purine nucleoside phosphorylase (PNP) activity. The ability of these agents to inhibit PNP has been ivestigated. All compounds were found to act as competitive (with inosine) inhibitors of PNP, with Ki values ranging from 0.2 to 290 .mu.M. The most potent of these analogues, 8-amino-9-benzylguanine, exhibited a Ki value that was 4-fold lower than that determined for the parent base, 8-aminoguanine. As a metabolically stable compound in human blood, 8-amino-9-benzylguanine was more effective than 8-aminoguanine at potentiating the toxicity of 2''-deoxyguanosine at potentiating the toxicity of 2''-deoxyguanosine to MOLT-4 T-lymphoblasts in culture. 8-Amino-9-benzylguanine is the most potent base or nucleoside inhibitor of human PNP reported to date, and it is a promising lead compound in the development of more effective PNP inhibitors.This publication has 17 references indexed in Scilit:
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