The Antiangiogenic Activity of Naturally Occurring and Synthetic Homoisoflavonoids from the Hyacinthaceae (sensu APGII)

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 (GI50 of 2.3 × 10–4 μM).

Funder

Funder name	Awards
University of Surrey, United Kingdom	PhD Scholarship
Daphne Jackson Trust, United Kingdom
Royal Society of Chemistry, United Kingdom
National Institutes of Health, United States / National Eye Institute, United States	NIH/NEI R01EY025641
International Retinal Research Foundation, United States
Research to Prevent Blindness, United States