Synthesis and Biological Evaluation of Novel Homoisoflavonoids for Retinal Neovascularization

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• 作者：Halesha D. Basavarajappa ; Bit Lee ; Hyungjun Lee ; Rania S. Sulaiman ; Hongchan An ; Carlos Maga帽a ; Mehdi Shadmand ; Alexandra Vayl ; Gangaraju Rajashekhar ; Eun-Yeong Kim ; Young-Ger Suh ; Kiho Lee ; Seung-Yong Seo ; Timothy W. Corson
• 刊名：Journal of Medicinal Chemistry
• 出版年：2015
• 出版时间：June 25, 2015
• 年：2015
• 卷：58
• 期：12
• 页码：5015-5027
• 全文大小：614K
• ISSN：1520-4804

文摘

Eye diseases characterized by excessive angiogenesis such as wet age-related macular degeneration, proliferative diabetic retinopathy, and retinopathy of prematurity are major causes of blindness. Cremastranone is an antiangiogenic, naturally occurring homoisoflavanone with efficacy in retinal and choroidal neovascularization models and antiproliferative selectivity for endothelial cells over other cell types. We undertook a cell-based structure鈥揳ctivity relationship study to develop more potent cremastranone analogues, with improved antiproliferative selectivity for retinal endothelial cells. Phenylalanyl-incorporated homoisoflavonoids showed improved activity and remarkable selectivity for retinal microvascular endothelial cells. A lead compound inhibited angiogenesis in vitro without inducing apoptosis and had efficacy in the oxygen-induced retinopathy model in vivo.