Design and Synthesis of Novel Xyloketal Derivatives and Their Vasorelaxing Activities in Rat Thoracic Aorta and Angiogenic Activities in Zebrafish Angiogenesis Screen
Design and Synthesis of Novel Xyloketal Derivatives and Their Vasorelaxing Activities in Rat Thoracic Aorta and Angiogenic Activities in Zebrafish Angiogenesis Screen
复制标题
新型木缩酮衍生物的设计和合成及其在大鼠胸主动脉中的血管舒张活性和斑马鱼血管生成筛选中的血管生成活性
DOI：
10.1021/jm1001502
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发表时间：
2010-06-24
影响因子：
7.3
通讯作者：
Lin, Yongcheng
中科院分区：
文献类型：
--
作者：
Xu, Zhongliang;Li, Yiying;Lin, Yongcheng
设计并合成了一系列新型木缩酮衍生物（1-21）。大多数的化合物表现出血管舒张作用60 mM氯化钾诱导的收缩大鼠离体主动脉环在浓度依赖性的方式，和行动是由内皮非依赖性和内皮依赖性机制介导的。与先导化合物3相比，化合物9、12、13、14、15和19显示出更高的血管舒张活性。此外，这些衍生物对oxLDL诱导的内皮细胞氧化损伤具有潜在的保护作用，并在HUVECs中增强NO的产生而无毒性作用。eNOS抑制剂L-NAME可完全抑制NO的释放。此外，在0.1、1和10 μ M下，3以浓度依赖性方式显著促进斑马鱼中的血管生成。化合物9、12、14、16、20和21显示出比3更强的血管生成活性。因此，木缩酮衍生物是具有多种药理学性质的独特化合物，可能在心血管疾病的治疗中具有潜在的意义。
A novel series of xyloketal derivatives (1-21) were designed and prepared. The majority of the compounds demonstrated vasorelaxation action on 60 mM KCl-induced contractions rat isolated aortic rings in a concentration-dependent manner, and the action is mediated by both endothelium-independent and endothelium-dependent mechanisms. Compounds 9, 12, 13, 14, 15, and 19 showed higher vasorelaxation activities comparing with the lead compound 3. In addition, these derivatives had potential protective action against oxLDL-induced endothelial oxidative injury and enhanced NO production in HUVECs without toxic effects. The NO release was completely inhibited by eNOS inhibitor L-NAME. Furthermore, 3 significantly promoted the angiogenesis in zebrafish in a concentration-dependent manner at 0.1, 1, and 10 mu M. Compounds 9, 12, 14, 16, 20, and 21 exhibited stronger angiogenic activities than 3. Therefore, xyloketal derivatives are unique compounds with multiple pharmacological properties and may have potential implications in the treatment of cardiovascular diseases.