Synthesis and Biological Evaluation of Novel Homoisoflavonoids for Retinal Neovascularization
| Autor: | Carlos Magaña, Timothy W. Corson, Young-Ger Suh, Eun Yeong Kim, Rania S. Sulaiman, Hongchan An, Halesha D. Basavarajappa, Gangaraju Rajashekhar, Alexandra Vayl, Mehdi Shadmand, Kiho Lee, Hyungjun Lee, Bit Lee, Seung-Yong Seo |
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| Rok vydání: | 2015 |
| Předmět: |
Angiogenesis
Angiogenesis Inhibitors Retinal Neovascularization Article Retina Mice chemistry.chemical_compound Drug Discovery medicine Animals Humans Cell Proliferation Chemistry Retinopathy of prematurity Retinal Diabetic retinopathy Anatomy Macular degeneration medicine.disease Isoflavones medicine.anatomical_structure Choroidal neovascularization Cancer research Molecular Medicine medicine.symptom Retinopathy |
| Zdroj: | Journal of Medicinal Chemistry. 58:5015-5027 |
| ISSN: | 1520-4804 0022-2623 |
| Popis: | 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-activity 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. |
| Databáze: | OpenAIRE |
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