Department of Oncology, 3970 Reservoir Road, Drug Discovery Program, Georgetown University Medical Center, Washington, DC 20057, United States.
Bioorg Med Chem. 2010 Jan 15;18(2):971-7. doi: 10.1016/j.bmc.2009.11.003. Epub 2009 Nov 10.
Chalcones represent a class of natural products that inhibits tubulin assembly. In this study we designed and synthesized boronic acid analogs of chalcones in an effort to compare biological activities with combretastatin A-4, a potent inhibitor of tubulin polymerization. Systematic evaluation of the positional effects of the carbonyl moiety towards inhibition of tubulin polymerization, cancer cell proliferation and angiogenesis revealed that placement of the carbonyl adjacent to the trimethoxybenzene A-ring resulted in more active compounds than when the carbonyl group was placed adjacent to the C-ring. Our study identified a boronic acid chalcone with inhibition towards 16 human cancer cell lines in the 10-200nM range, and another three cell lines with GI(50)-values below 10nM. Furthermore, this drug has significant anti-angiogenesis effects demonstrated by HUVEC tube formation and aortic ring assay.
查耳酮是一类天然产物，能抑制微管蛋白的组装。在这项研究中，我们设计并合成了查耳酮的硼酸类似物，以努力比较其与 combretastatin A-4 的生物学活性，后者是一种有效的微管聚合抑制剂。系统评估羰基在抑制微管蛋白聚合、癌细胞增殖和血管生成方面的位置效应表明，将羰基置于三甲氧基苯 A 环附近的位置会产生比将羰基置于 C 环附近时更具活性的化合物。我们的研究确定了一种硼酸查尔酮，对 16 个人类癌细胞系的抑制作用在 10-200nM 范围内，另外三个细胞系的 GI(50)值低于 10nM。此外，该药物具有显著的抗血管生成作用，表现在 HUVEC 管形成和主动脉环测定中。
