title: 3D-QSAR studies on a series of dihydroorotate dehydrogenase inhibitors: analogues of the active metabolite of leflunomide.
abstract: The active metabolite of the novel immunosuppressive agent leflunomide has been shown to inhibit the enzyme dihydroorotate dehydrogenase (DHODH). This enzyme catalyzes the fourth step in de novo pyrimidine biosynthesis. Self-organizing molecular field analysis (SOMFA), a simple three-dimensional quantitative structure-activity relationship (3D-QSAR) method is used to study the correlation between the molecular properties and the biological activities of a series of analogues of the active metabolite. The statistical results, cross-validated r(CV) (2) (0.664) and non cross-validated r(2) (0.687), show a good predictive ability. The final SOMFA model provides a better understanding of DHODH inhibitor-enzyme interactions, and may be useful for further modification and improvement of inhibitors of this important enzyme.
authors.affiliation: College of Science, Beijing University of Chemical Technology, 15 Beisanhuan East Road, Chaoyang District, Beijing 100029, China; E-Mail: wulianhmy2008@163.com (M.-Y.H.).
authors.forename: Shun-Lai
authors.initials: SL
authors.lastname: Li
authors.forename: Mao-Yu
authors.initials: MY
authors.lastname: He
authors.forename: Hong-Guang
authors.initials: HG
authors.lastname: Du
mesh_terms: D000090722:Dihydroorotate Dehydrogenase; D004791:Enzyme Inhibitors / Q000737:chemistry*; D007166:Immunosuppressive Agents / Q000737:chemistry*; D007555:Isoxazoles / Q000737:chemistry*; D000077339:Leflunomide; D008958:Models, Molecular; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000037:antagonists & inhibitors*; D021281:Quantitative Structure-Activity Relationship
chemical_list: D000090722:Dihydroorotate Dehydrogenase; D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D007555:Isoxazoles; D044925:Oxidoreductases Acting on CH-CH Group Donors; D000077339:Leflunomide