School of Life Sciences, Pharmacy and Chemistry , Kingston University , Kingston-upon-Thames , KT1 2EE , U.K.
Natural Products Research Group, Department of Chemistry, Faculty of Engineering and Physical Sciences , University of Surrey , Guildford , GU2 7XH , U.K.
J Nat Prod. 2019 May 24;82(5):1227-1239. doi: 10.1021/acs.jnatprod.8b00989. Epub 2019 Apr 5.
Excessive blood vessel formation in the eye is implicated in wet age-related macular degeneration, proliferative diabetic retinopathy, neovascular glaucoma, and retinopathy of prematurity, which are major causes of blindness. Small molecule antiangiogenic drugs are strongly needed to supplement existing biologics. Homoisoflavonoids have been previously shown to have potent antiproliferative activities in endothelial cells over other cell types. Moreover, they demonstrated a strong antiangiogenic potential in vitro and in vivo in animal models of ocular neovascularization. Here, we tested the antiangiogenic activity of a group of naturally occurring homoisoflavonoids isolated from the family Hyacinthaceae and related synthetic compounds, chosen for synthesis based on structure-activity relationship observations. Several compounds showed interesting antiproliferative and antiangiogenic activities in vitro on retinal microvascular endothelial cells, a disease-relevant cell type, with the synthetic chromane, 46, showing the best activity (GI of 2.3 × 10 μM).
眼部过度血管生成与湿性年龄相关性黄斑变性、增生性糖尿病视网膜病变、新生血管性青光眼和早产儿视网膜病变有关，这些都是导致失明的主要原因。需要小分子抗血管生成药物来补充现有的生物制剂。先前的研究表明，同型异黄酮类化合物在血管内皮细胞中的增殖活性强于其他细胞类型。此外，它们在体外和体内动物模型的眼部新生血管化中表现出很强的抗血管生成潜力。在这里，我们测试了一组从风信子科和相关合成化合物中分离出的天然存在的同型异黄酮类化合物的抗血管生成活性，选择这些化合物进行合成是基于结构-活性关系的观察。一些化合物在视网膜微血管内皮细胞（一种与疾病相关的细胞类型）上显示出有趣的体外增殖和抗血管生成活性，其中合成的色满，46，表现出最好的活性（GI 为 2.3×10μM）。
