Hannah Whitmore1, Kamakshi Sishtla2, Walter Knirsch3, Jacky L Andriantiana4, Sianne Schwikkard5, Eduard Mas-Claret1, Sarah M Nassief1, Sani M Isyaka6, Timothy W Corson7, Dulcie A Mulholland8. 1. Natural Products Research Group, Department of Chemistry, University of Surrey, Guildford GU2 7XH, United Kingdom. 2. Eugene and Marilyn Glick Eye Institute, Department of Ophthalmology, Indiana University School of Medicine, 1160 W. Michigan St., Indianapolis, IN 46202, USA. 3. Institute of Plant Sciences, NAWI Graz, Karl-Franzens University Graz, Holteigasse 6, A-8010 Graz, Austria. 4. Parc Botanique et Zoologique de Tsimbazaza, Rue Fernand Kassanga, Antananarivo 101, Madagascar. 5. School of Life Sciences, Pharmacy and Chemistry, Kingston University, Kingston-upon-Thames KT1 2EE, United Kingdom. 6. Natural Products Research Group, Department of Chemistry, University of Surrey, Guildford GU2 7XH, United Kingdom; School of Chemistry and Physics, University of KwaZulu-Natal, Durban, South Africa. 7. Eugene and Marilyn Glick Eye Institute, Department of Ophthalmology, Indiana University School of Medicine, 1160 W. Michigan St., Indianapolis, IN 46202, USA. Electronic address: tcorson@iu.edu. 8. Natural Products Research Group, Department of Chemistry, University of Surrey, Guildford GU2 7XH, United Kingdom; School of Chemistry and Physics, University of KwaZulu-Natal, Durban, South Africa. Electronic address: d.mulholland@surrey.ac.uk.
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.
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.
Authors: Sianne Schwikkard; Alaa Alqahtani; Walter Knirsch; Wolfgang Wetschnig; Andrius Jaksevicius; Elizabeth I Opara; Moses K Langat; Jackie L Andriantiana; Dulcie A Mulholland Journal: J Nat Prod Date: 2017-01-04 Impact factor: 4.050
Authors: Halesha D Basavarajappa; Bit Lee; Seung-Yong Seo; Timothy W Corson; Hyungjun Lee; Rania S Sulaiman; Hongchan An; Carlos Magaña; Mehdi Shadmand; Alexandra Vayl; Gangaraju Rajashekhar; Eun-Yeong Kim; Young-Ger Suh; Kiho Lee Journal: J Med Chem Date: 2015-06-16 Impact factor: 7.446