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

Sianne Schwikkard, Hannah Whitmore, Kamakshi Sishtla, Rania S. Sulaiman, Trupti Shetty, Halesha D. Basavarajappa, Catherine Waller, Alaa Alqahtani, Lennart Frankemoelle, Andy Chapman, Neil Crouch, Wolfgang Wetschnig, Walter Knirsch, Jacky Andriantiana, Eduard Mas-Claret, Moses K. Langat, Dulcie Mulholland, Timothy Corson

Research output: Contribution to journalArticle

2 Citations (Scopus)

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).

Original languageEnglish (US)
JournalJournal of Natural Products
DOIs
StatePublished - Jan 1 2019
Externally publishedYes

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Endothelial cells
Endothelial Cells
Neovascular Glaucoma
Artificial Cells
Retinopathy of Prematurity
Blood vessels
Macular Degeneration
Diabetic Retinopathy
Blindness
Structure-Activity Relationship
Biological Products
Blood Vessels
Animals
Animal Models
Molecules
Pharmaceutical Preparations
In Vitro Techniques
Asparagaceae

ASJC Scopus subject areas

  • Analytical Chemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine
  • Organic Chemistry

Cite this

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; Corson, Timothy.

In: Journal of Natural Products, 01.01.2019.

Research output: Contribution to journalArticle

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 & Corson, T 2019, 'The Antiangiogenic Activity of Naturally Occurring and Synthetic Homoisoflavonoids from the Hyacinthaceae (sensu APGII)', Journal of Natural Products. https://doi.org/10.1021/acs.jnatprod.8b00989
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 ; Corson, Timothy. / The Antiangiogenic Activity of Naturally Occurring and Synthetic Homoisoflavonoids from the Hyacinthaceae (sensu APGII). In: Journal of Natural Products. 2019.
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