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

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 (GI50 of 2.3 × 10–4 μM).

Enantioselective Synthesis of Homoisoflavanones by Asymmetric Transfer Hydrogenation and Their Biological Evaluation for Antiangiogenic Activity

“…Moreover, chiral ( R )- 2 and ( S )- 2 were coupled with two different enantiomers of Boc-phenylalanine under EDCI-mediated conditions to provide four stereoisomers of anti-angiogenic homoisoflavanone 3 : ( R , R )-, ( S , R )-, ( R , S )-, and ( S , S )- 3 , respectively. Chiral 3-benzyl-chromanes were considered as attractive derivatives of homoisoflavonoids; a racemic 3-benzyl-chromane 10 reported recently showed potent activity . Thus, ( S )-3-benzyl-chromane ( S )- 10 was obtained from (3 R ,4 R )- 9a by treatment with triethylsilane.…”

A Comprehensive Review on Chemotaxonomic and Phytochemical Aspects of Homoisoflavonoids, as Rare Flavonoid Derivatives

“…Moreover, some identified HIFs were isolated from the bulb parts of other Eucomis species. The following extracts were investigated: E. autumnalis (1-butanol) [ 66 ], E. comosa (EtOAc) [ 65 ], E. montana (CH 2 Cl 2 , EtOAc, and MeOH) [ 67 ], E. schijffii (CH 2 Cl 2 ) [ 65 ], E. vandermerwei (CH 2 Cl 2 and MeOH) [ 68 ], and E. zambesiaca (MeOH) [ 68 ].…”

Bufadienolides and anti-angiogenic homoisoflavonoids from Rhodocodon cryptopodus, Rhodocodon rotundus and Rhodocodon cyathiformis

“…Small molecule antiangiogenic drugs are urgently needed to supplement the existing available biologies, including drugs such as bevacizumab, ranibizumab, and aflibercept, which target the vascular endothelial growth factor (VEGF) [4]. Homoisoflavonoids, a class of compounds commonly found in the Scilloideae subfamily of the Asparagaceae family, have been shown previously to have potent anti-proliferative activities in endothelial cells over other cell types [17]. Moreover, they demonstrated a strong antiangiogenic potential in vitro and in vivo in animal models of ocular neovascularization [23].…”