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Inhibition of Bilirubin UDP-glucuronosyltransferase: A Comparative Molecular Field Analysis (CoMFA)

1996; Wiley; Volume: 15; Issue: 5 Linguagem: Inglês

10.1002/qsar.19960150503

1521-3838

Mourad Said, Jean-Claude Ziegler, Jacques Magdalou, A. Elass, Gérard Vergoten,

Liver Disease Diagnosis and Treatment

Abstract Two series of compounds structurally related to phenolphthalein and triphenylalkyl carboxylic acid were tested as inhibitors of bilirubin glucuronidation catalyzed by rat liver microsomal UDP‐glucuronosyltransferase, and analyzed by the CoMFA method in order to predict the inhibitory potency of these structures and afford a three dimensional structure of the bilirubin binding site. These substances could inhibit bilirubin glucuronidation to different extents. Their inhibitory potency was quantitated in terms of I 50 values. The best inhibitors exhibited competitive inhibition. The 3D‐QSAR results led to a fairly good prediction of the inhibitory potency of these two series of compounds. They indicate a correlation between the inhibitory activity of the glucuronidation reaction and the steric and electrostatic fields with a relative contribution of 43% and 57%, respectively.