Structure-activity relationship of pyrimidine base analogs as ligands of orotate phosphoribosyltransferase.

Abstract:

:Eighty pyrimidine base analogs were evaluated as inhibitors of mouse liver orotate phosphoribosyltransferase (OPRTase, EC 2.4.2.10). Based on these findings and an extensive literature review, a structure-activity relationship has been formulated for the binding of pyrimidine base analogs to OPRTase. This study provides a basis for the rational design of new inhibitors of this enzyme, and several such compounds are proposed. Additionally, 4,6-dihydroxypyrimidine has been found to be a potent OPRTase inhibitor. Eleven OPRTase inhibitors were also evaluated as inhibitors of orotidine 5'-monophosphate decarboxylase (ODCase, EC 4.1.2.23). 5-Azauracil, 5-azaorotate, and barbituric acid inhibited ODCase significantly only after preincubation with PRPP and MgCl2 in the presence of cytosol.

journal_name

Biochem Pharmacol

journal_title

Biochemical pharmacology

authors

Niedzwicki JG,Iltzsch MH,el Kouni MH,Cha S

doi

10.1016/0006-2952(84)90710-x

subject

Has Abstract

pub_date

1984-08-01 00:00:00

pages

2383-95

issue

15

eissn

0006-2952

issn

1873-2968

pii

0006-2952(84)90710-X

journal_volume

33

pub_type

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