title: Dihydroorotate dehydrogenase inhibitors: quantitative structure-activity relationship analysis.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles 90033, USA. sren@hsc.usc.edu
authors.forename: S
authors.initials: S
authors.lastname: Ren
authors.forename: S K
authors.initials: SK
authors.lastname: Wu
authors.forename: E J
authors.initials: EJ
authors.lastname: Lien
mesh_terms: D000818:Animals; D002264:Carboxylic Acids / Q000737:chemistry / Q000494:pharmacology; D000090722:Dihydroorotate Dehydrogenase; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D051379:Mice; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D044925:Oxidoreductases Acting on CH-CH Group Donors; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D002264:Carboxylic Acids; D000090722:Dihydroorotate Dehydrogenase; D004791:Enzyme Inhibitors; D010088:Oxidoreductases; D044925:Oxidoreductases Acting on CH-CH Group Donors