University of Surrey

Test tubes in the lab Research in the ATI Dance Research

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

Whitmore, Hannah, Sishtla, Kamakshi, Knirsch, Walter, Andriantiana, Jacky L., Schwikkard, Sianne, Mas-Claret, Eduard, Nassief, Sarah M., Isyaka, Sani M., Corson, Timothy W. and Mulholland, Dulcie A. (2020) Bufadienolides and anti-angiogenic homoisoflavonoids from Rhodocodon cryptopodus, Rhodocodon rotundus and Rhodocodon cyathiformis Fitoterapia, 141, 104479.

[img] Text
Bufadienolides and anti-angiogenic homoisoflavonoids - AAM.pdf - Accepted version Manuscript
Restricted to Repository staff only until 10 January 2021.

Download (898kB)

Abstract

Background

Homoisoflavonoids have been shown to have potent anti-proliferative activities in endothelial cells over other cell types and have demonstrated a strong antiangiogenic potential in vitro and in vivo in animal models of ocular neovascularization. Three species of Rhodocodon (Scilloideaea subfamily of the Asparagaceae family), endemic to Madagascar, R. cryptopodus, R. rotundus and R. cyathiformis, were investigated.

Purpose

To isolate and test homoisoflavonoids for their antiangiogenic activity against human retinal microvascular endothelial cells (HRECs), as well as specificity against other ocular cell lines.

Methods

Plant material was extracted at room temperature with EtOH. Compounds were isolated using flash column chromatography and were identified using NMR and CD spectroscopy and HRESIMS. Compounds were tested for antiproliferative effects on primary human microvascular retinal endothelial cells (HRECs), ARPE19 retinal pigment epithelial cells, 92–1 uveal melanoma cells, and Y79 retinoblastoma cells. HRECs exposed to compounds were also tested for migration and tube formation ability.

Results

Two homoisoflavonoids, 3S-5,7-dihydroxy-(3′-hydroxy-4′-methoxybenzyl)-4-chromanone (1) and 3S-5,7-dihydroxy-(4′-hydroxy-3′-methoxybenzyl)-4-chromanone (2), were isolated along with four bufadienolides. Compound 1 was found to be non-specifically antiproliferative, with GI50 values ranging from 0.21–0.85 μM across the four cell types, while compound 2 showed at least 100-fold specificity for HRECs over the other tested cell lines. Compound 1, with a 3S configuration, was 700 times more potent that the corresponding 3R enantiomer recently isolated from a Massonia species.

Conclusion

Select homoisoflavonoids have promise as antiangiogenic agents that are not generally cytotoxic.

Item Type: Article
Divisions : Faculty of Engineering and Physical Sciences > Chemistry
Authors :
NameEmailORCID
Whitmore, Hannahh.whitmore@surrey.ac.uk
Sishtla, Kamakshi
Knirsch, Walter
Andriantiana, Jacky L.
Schwikkard, Sianne
Mas-Claret, Eduarde.masclaret@surrey.ac.uk
Nassief, Sarah M.s.nassiefabdou@surrey.ac.uk
Isyaka, Sani M.
Corson, Timothy W.
Mulholland, Dulcie A.D.Mulholland@surrey.ac.uk
Date : March 2020
Funders : University of Surrey, Daphne Jackson Trust, Royal Society of Chemistry
DOI : 10.1016/j.fitote.2020.104479
Copyright Disclaimer : © 2020. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
Uncontrolled Keywords : Rhodocodon; Homoisoflavonoids; Bufadienolides; Anti-angiogenic; Neovascularization; Endothelial cells
Depositing User : Clive Harris
Date Deposited : 01 Sep 2020 13:59
Last Modified : 01 Sep 2020 13:59
URI: http://epubs.surrey.ac.uk/id/eprint/858521

Actions (login required)

View Item View Item

Downloads

Downloads per month over past year


Information about this web site

© The University of Surrey, Guildford, Surrey, GU2 7XH, United Kingdom.
+44 (0)1483 300800