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The Design, Synthesis, Biological Evaluations and QSAR Studies of Emodin Derivatives Targeted at MMPs

Author: WangXingPo
Tutor: XuWenFang
School: Shandong University
Course: Medicinal Chemistry
Keywords: rational drug design matrix metallloproteinaes inhibitors Emodin chemical synthesis anti-tumor activity quantitative structure-activity relationships CoMFA
CLC: R284
Type: PhD thesis
Year: 2006
Downloads: 347
Quote: 0
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Abstract


The majority of cancer-related deaths results from tumor cell invasion and metastasis. The processes of invasion and metastasis of tumor cells are very complicated, in which the degradation of basement membrane and stromal tissue is essential for migration of endothelial cells which needed to form new blood vessels and also critical for the entry and exit of tumor cells into existing blood vessels which are necessary for metastasis. The degradation of basement membrane and ECM (extracellular matrix) must be catalyzed by a series of proteinase in which a class of hydrolytic proteases named matrix metalloproteinases(MMPs) plays a pivotal role.The relative level of individual MMPs tends to increase with increasing tumor stage. Transfection of selected MMPs into cancer cells can increase the generation of distant metastases in vivo.Inhibition and regulation of the activity of MMPs will control the invasion andmetastasis of tumor cell, thus prevent the process of tumor growth and progression. For these reasons, MMPs are considered to be key enzymes involved inangiogenesis and become an attractive therapeutic target.Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is a biological active constituent of genus Rhamnus herb. Pharmacological studies have demonstrated that

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