Abstract
Purpose. 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.
Methods. 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.
Results. 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.
Conclusions. 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.
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Ren, S., Wu, S.K. & Lien, E.J. Dihydroorotate Dehydrogenase Inhibitors: Quantitative Structure-activity Relationship Analysis. Pharm Res 15, 286–295 (1998). https://doi.org/10.1023/A:1011978904905
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DOI: https://doi.org/10.1023/A:1011978904905