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

Schwikkard, Sianne, Whitmore, Hannah, Sishtla, Kamakshi, Sulaiman, Rania S., Shetty, Trupti, Basavarajappa, Halesha D., Waller, Catherine, Alqahtani, Alaa, Frankemoelle, Lennart, Chapman, Andy , Crouch, Neil, Wetschnig, Wolfgang, Knirsch, Walter, Andriantiana, Jacky, Mas-Claret, Eduard, Langat, Moses K., Mulholland, Dulcie and Corson, Timothy W. (2019) The Antiangiogenic Activity of Naturally Occurring and Synthetic Homoisoflavonoids from the Hyacinthaceae (sensu APGII) Journal of Natural Products.

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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).

Item Type: Article
Divisions : Faculty of Engineering and Physical Sciences > Chemistry
Authors :
NameEmailORCID
Schwikkard, Sianne
Whitmore, Hannahh.whitmore@surrey.ac.uk
Sishtla, Kamakshi
Sulaiman, Rania S.
Shetty, Trupti
Basavarajappa, Halesha D.
Waller, Catherine
Alqahtani, Alaa
Frankemoelle, Lennart
Chapman, Andy
Crouch, Neil
Wetschnig, Wolfgang
Knirsch, Walter
Andriantiana, Jacky
Mas-Claret, Eduard
Langat, Moses K.
Mulholland, DulcieD.Mulholland@surrey.ac.uk
Corson, Timothy W.
Date : 2019
Funders : University of Surrey, National Institutes of Health
DOI : 10.1021/acs.jnatprod.8b00989
Copyright Disclaimer : Copyright © 2019 American Chemical Society and American Society of Pharmacognosy
Depositing User : Clive Harris
Date Deposited : 26 Apr 2019 09:59
Last Modified : 06 Apr 2020 02:08
URI: http://epubs.surrey.ac.uk/id/eprint/851698

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