Synthesis and Biological Evaluation of Novel Homoisoflavonoids for Retinal Neovascularization

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.