1. The Antiangiogenic Activity of Naturally Occurring and Synthetic Homoisoflavonoids from the Hyacinthaceae ( sensu APGII).
- Author
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Schwikkard S, Whitmore H, Sishtla K, Sulaiman RS, Shetty T, Basavarajappa HD, Waller C, Alqahtani A, Frankemoelle L, Chapman A, Crouch N, Wetschnig W, Knirsch W, Andriantiana J, Mas-Claret E, Langat MK, Mulholland D, and Corson TW
- Subjects
- Cell Proliferation drug effects, Endothelial Cells drug effects, Human Umbilical Vein Endothelial Cells drug effects, Humans, Molecular Structure, Plant Extracts chemistry, Plant Extracts pharmacology, Plant Roots chemistry, Retinal Neovascularization prevention & control, Structure-Activity Relationship, Angiogenesis Inhibitors pharmacology, Asparagaceae chemistry, Flavonoids pharmacology
- Abstract
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 (GI
50 of 2.3 × 10-4 μM).- Published
- 2019
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