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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 (GI50of 2.3 × 10–4μM).

The genus Rhodocodon(Hyacinthaceae sensu APG II) is endemic to Madagascar, and its phytochemistry has not been described previously. The phytochemistry of three species in this genus has been investigated, and eight compounds, including three bufadienolides (compounds 1, 4, and 5), a norlignan (2), and four homoisoflavonoids (compounds 3and 6–8), have been isolated and identified. Compounds 1–3and 6–8have not been described previously. The COX-2 inhibitory activity of compound 6and compound 7acetate (compound 7A) was investigated on isolated colorectal cancer cells. Compounds 6and 7Ainhibited COX-2 by 10% and 8%, respectively, at a concentration of 12.5 μM compared to 12% for 1 mM aspirin (the positive control).