PDF(1939 KB)
PDF(1939 KB)
PDF(1939 KB)
COX-2/DHODH双重抑制剂存在可行性的初步对接虚拟筛选研究
Feasibility study of the existence of dual inhibitors of COX-2/DHODH based on virtual screening
首次开展了探索环氧合酶-2(COX-2)和二氢乳清酸脱氢酶(DHODH)双重抑制剂存在的可行性研究工作。通过自建COX-2抑制剂数据库，采用虚拟筛选方法，以DHODH的晶体结构为靶标，对建的COX-2抑制剂数据库进行对接虚拟筛选，筛选出多个对DHODH可能有抑制作用并且具有COX-抑制活性的分子。研究表明，现有数据库中的25000系列、7000系列、26000系列以及33000系列的抑制剂最有可能成为DHODH和COX-2的双抑制剂，特别是其中的2500、7004和7006这三个抑制剂，具有进一步实验研究的价值。
［1］Kurumbail R G, Stevens A M, Gierse J K, et al. Structural basis for selective inhibition of cyclooxygenase2 by antiinflammatory agents［J］. Nature,1997, 384: 644-648.
［2］Uiu S, Neidhardt E A, Grossman T H, et al. Structures of human dihydrooro
tate dehydrogenase in complex with antiproliferative agents［J］. Structure Fold
Des, 2000, 8: 25-33.
［3］Lyne P D. Structurebased virtual screening: An overview［J］. DrugDiscov Today, 2002, 7: 1047-1055.
［4］Zsolt Z, Darryl R, Aniko S, et al. eHiTS: An innovative approach to the docking and scoring function problems[JP2]［J］. Current Protein and Peptide Science,2006, 7: 421-[JP]435.
［5］Zsolt Z, Darryl R, Aniko S, et al. eHiTS: A new fast, exhaustive flexible
ligand docking system［J］. J Mol Grap Mode, 2007,26(1):198-212.
［6］Tímea P, Csaba M, Istvn S, et al. Impact of Ligand Protonation on Virtual Screening againstSecretase [JP2](BACE1) ［J］. J Chem Inf Model, 2007,47 (6):2366-[JP]2373.
［7］〓Englebienne P, Fiaux H, Kuntz D, et al. Evaluation of docking programs fo
r predicting binding of Golgi alphamannosidase II inhibitors: A comparison wit
h crystallography［J］. Proteins, 2007,69(1):160-176.
［8］Carlson R P. Newer immunosuppressive drugs and other agents for the treatment of rheumatoid arthritisAn update［J］. Exp Opin Invest Drugs,1995, 4(9):
853-859.
［9］Elizabeth A K, Philip T H, David P K, et al. Synthesis, StructureActivi
ty Relationships, and Pharmacokinetic Properties of Dihydroorotate DehydrogenaseInhibitors: 2Cyano3cyclopropyl3hydroxyN［3′methyl4′(trifluoromethyl)phenyl］propenamide and Related Compounds［J］. J Med Chem,1996, 39(23): 4608-4621.〖ZK)〗
［10］Thompson M. A. ArgusLab 4.0.1［CP/OL］. Seattle, WA: Planaria Software LLC, 2004, ［20070328］. http:∥www.arguslab.com.
［11］Wallace A C,Laskowski R A,Thornton J M. LIGPLOT: A program to generate schematic diagrams of proteinligand interactions［J］. Prot Eng,1995, 8: 127-134.
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