Ren S, Wu S K, Lien E J
Department of Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles 90033, USA.
Pharm Res. 1998 Feb;15(2):286-95. doi: 10.1023/a:1011978904905.
The main purpose of this study is to analyze the quantitative structure-activity relationship of two series of dihydroorotate dehydrogenase inhibitors (leflunomide and quinoline carboxylic acid analogues), and to determine the structural requirements for optimum activity of these analogues.
A new CQSAR program was used in deriving regression equations and calculating the octanol/water partition coefficient and the molar refractivity values. The molecular modeling was performed using the HyperChem program.
Statistically significant correlations were obtained using a combination of 3-4 parameters. The structural requirements for optimum activity and critical regions for the inhibitory activity of dihydroorotate dehydrogenase were identified.
The quantitative structure-activity relationship analysis demonstrated that two series of dihydroorotate dehydrogenase inhibitors may bind to different binding sites on the enzyme. These results provide a better understanding of dihydroorotate dehydrogenase inhibitor-enzyme interactions, and may be useful for further modification and improvement of inhibitors of this important enzyme.
