Synthesis and Biological Evaluation of Novel Homoisoflavonoids for Retinal Neovascularization

Halesha D. Basavarajappa, Bit Lee, Hyungjun Lee, Rania S. Sulaiman, Hongchan An, Carlos Magaña, Mehdi Shadmand, Alexandra Vayl, Gangaraju Rajashekhar, Eun Yeong Kim, Young Ger Suh, Kiho Lee, Seung Yong Seo, Timothy W. Corson

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)5015-5027
Number of pages13
JournalJournal of Medicinal Chemistry
Volume58
Issue number12
DOIs
StatePublished - Jun 25 2015

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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    Basavarajappa, H. D., Lee, B., Lee, H., Sulaiman, R. S., An, H., Magaña, C., Shadmand, M., Vayl, A., Rajashekhar, G., Kim, E. Y., Suh, Y. G., Lee, K., Seo, S. Y., & Corson, T. W. (2015). Synthesis and Biological Evaluation of Novel Homoisoflavonoids for Retinal Neovascularization. Journal of Medicinal Chemistry, 58(12), 5015-5027. https://doi.org/10.1021/acs.jmedchem.5b00449