Structural Modification of Honokiol, a Biphenyl Occurring in Magnolia officinalis: the Evaluation of Honokiol Analogues as Inhibitors of Angiogenesis and for Their Cytotoxicity and Structure鈥揂ctivity

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• 作者：Liang Ma ; Jinying Chen ; Xuewei Wang ; Xiaolin Liang ; Youfu Luo ; Wei Zhu ; Tianen Wang ; Ming Peng ; Shucai Li ; Shi Jie ; Aihua Peng ; Yuquan Wei ; Lijuan Chen
• 刊名：Journal of Medicinal Chemistry
• 出版年：2011
• 出版时间：October 13, 2011
• 年：2011
• 卷：54
• 期：19
• 页码：6469-6481
• 全文大小：1133K
• 年卷期：v.54,no.19(October 13, 2011)
• ISSN：1520-4804

文摘

Honokiol, widely known as an antitumor agent, has been used as an antiangiogenesis drug lead. In this paper, 47 honokiol analogues and derivatives were investigated for their antiangiogenic activity by application of the transgenic zebrafish screening model, antiproliferative and cytotoxic activity against HUVECs, and three tumor cell lines by MTT assay. 3鈥?5-Diallyl-2,4鈥?dihydroxy-[1,1鈥?biphen-yl]-3,5鈥?dicarbaldehyde (8c) was found to suppress the newly grown segmental vessels from the dorsal aorta of zebrafish and prevent inappropriate vascularization as well as exhibit more potent inhibitory effects on the proliferation of HUVECs, A549, HepG2, and LL/2 cells (IC₅₀ = 15.1, 30.2, 10.7, and 21.7 渭M, respectively) than honokiol (IC₅₀ = 52.6, 35.0, 16.5, and 65.4 渭M, respectively). Analogue 8c also effectively inhibited the migration and capillary-like tube formation of HUVECs in vitro. The antiangiogenic effect and antiproliferative activity of these structurally modified honokiol analogues and derivatives have led to the establishment of a structure鈥揳ctivity relationship.