Quantitative structure-activity relationships of the metabolism of drugs by uridine diphosphate glucuronosyltransferase.

Quantitative structure-activity relationships of the metabolism of drugs by uridine diphosphate (UDP)-glucuronosyltransferase have been investigated. It is observed that most of the variation in the rate of glucuronidation of phenols, thiols, and some other miscellaneous compounds can be accounted for by the lipophilic property of the molecules. The results are consistent with the previous finding with primary and secondary alcohols, and benzoic acids. The optimum lipophilicity for these compounds undergoing metabolism by UDP-glucuronosyltransferase appears to be a log P of 2.

[1]  C. Hansch,et al.  The QSAR paradigm in the design of less toxic molecules. , 1984, Drug metabolism reviews.

[2]  C. Hansch,et al.  Structure--activity correlations in the metabolism of drugs. , 1968, Archives of biochemistry and biophysics.

[3]  D. Benford,et al.  Observations on the accessibility of acceptor substrates to the active centre of UDP-glucuronosyltransferase in vitro. , 1976, Biochimica et biophysica acta.

[4]  G. Wishart.  Demonstration of functional heterogeneity of hepatic uridine diphosphate glucuronosyltransferase activities after administration of 3-methylcholanthrene and phenobarbital to rats. , 1978, The Biochemical journal.

[5]  H. Illing,et al.  Mechanism of biosynthesis of thio- -D-glucuronides and thio- -D-glucosides. , 1972, The Biochemical journal.

[6]  C. Hansch,et al.  Lipophilic character and biological activity of drugs. II. The parabolic case. , 1973, Journal of pharmaceutical sciences.

[7]  M. Green,et al.  UDP-glucuronosyltransferases in the metabolic disposition of xenobiotics. , 1989, Drug metabolism reviews.

[8]  G. Mulder,et al.  A rapid NAD+-linked assay for microsomal uridine diphosphate glucuronyltransferase of rat liver and some observations on substrate specificity of the enzyme. , 1975, The Biochemical journal.

[9]  P. B. Wood,et al.  Kinetic studies of the metabolism of foreign organic compounds. III. The conjugation of phenols with glucuronic acid. , 1952, The Biochemical journal.

[10]  A. Leo,et al.  Hydrophobicity and central nervous system agents: on the principle of minimal hydrophobicity in drug design. , 1987, Journal of pharmaceutical sciences.