Combretastatin Dinitrogen-Substituted Stilbene Analogues as Tubulin-Binding and Vascular-Disrupting Agents

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• 作者：Rogelio Siles ; J. Freeland Ackley ; Mallinath B. Hadimani ; John J. Hall ; Benon E. Mugabe ; Rajsekhar Guddneppanavar ; Keith A. Monk ; Jean-Charles Chapuis ; George R. Pettit ; David J. Chaplin ; Klaus Edvard
• 刊名：Journal of Natural Products
• 出版年：2008
• 出版时间：March 2008
• 年：2008
• 卷：71
• 期：3
• 页码：313 - 320
• 全文大小：187K
• 年卷期：v.71,no.3(March 2008)
• ISSN：1520-6025

文摘

Several stilbenoid compounds having structural similarity to the combretastatin group of natural products and characterized by the incorporation of two nitrogen-bearing groups (amine, nitro, serinamide) have been prepared by chemical synthesis and evaluated in terms of biochemical and biological activity. The 2′,3′-diamino B-ring analogue 17 demonstrated remarkable cytotoxicity against selected human cancer cell lines in vitro (average GI₅₀ = 13.9 nM) and also showed good activity in regard to inhibition of tubulin assembly (IC₅₀ = 2.8 µM). In addition, a single dose (10 mg/kg) of compound 17 caused a 40% tumor-selective blood flow shutdown in tumor-bearing SCID mice at 24 h, thus suggesting the potential value of this compound and its corresponding salt formulations as new vascular-disrupting agents.