Planta Med 2019; 85(18): 1519
DOI: 10.1055/s-0039-3400008
Main Congress Poster
Poster Session 2
© Georg Thieme Verlag KG Stuttgart · New York

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

E Mas-Claret
1   Natural Products Research Group, Department of Chemistry, Faculty of Engineering and Physical Sciences, University of Surrey,, Guildford, Surrey, GU2 7XH, UK
,
H Whitmore
1   Natural Products Research Group, Department of Chemistry, Faculty of Engineering and Physical Sciences, University of Surrey,, Guildford, Surrey, GU2 7XH, UK
,
K Sishtla
2   Eugene and Marilyn Glick Eye Institute, Department of Ophthalmology, Indiana University School of Medicine,, 1160 W. Michigan St., Indianapolis, IN 46202, USA
,
W Knirsch
3   Institute of Plant Sciences, NAWI Graz, Karl-Franzens University Graz,, Holteigasse 6, A-8010, Graz, Austria
,
JL Andriantiana
4   Parc Botanique et Zoologique de Tsimbazaza, Rue Fernand Kassanga,, Antananarivo 101, Madagascar
,
S Schwikkard
5   School of Life Sciences, Pharmacy and Chemistry, Kingston University,, Kingston-upon-Thames, KT1 2EE, UK
,
SM Nassief
1   Natural Products Research Group, Department of Chemistry, Faculty of Engineering and Physical Sciences, University of Surrey,, Guildford, Surrey, GU2 7XH, UK
,
SM Isyaka
1   Natural Products Research Group, Department of Chemistry, Faculty of Engineering and Physical Sciences, University of Surrey,, Guildford, Surrey, GU2 7XH, UK
,
TW Corson
2   Eugene and Marilyn Glick Eye Institute, Department of Ophthalmology, Indiana University School of Medicine,, 1160 W. Michigan St., Indianapolis, IN 46202, USA
,
DA Mulholland
1   Natural Products Research Group, Department of Chemistry, Faculty of Engineering and Physical Sciences, University of Surrey,, Guildford, Surrey, GU2 7XH, UK
› Author Affiliations
Further Information

Publication History

Publication Date:
20 December 2019 (online)

Also available at
 

Abnormal retinal vascularization is the leading cause of conditions associated with vision loss in developed countries, such as age-related macular degeneration (AMD) or diabetic retinopathy. [1] The current approach for their treatment is based on inhibitors of the vascular endothelial growth factor (VEGF). However, up to 30% of patients are non-responsive to these drugs, which are also linked to ocular and systemic side effects. [2] For that reason, there is an urgent need for small antiangiogenic molecule leads to supplement the existing biologics. Homoisoflavonoids have previously shown potent antiangiogenic activity in vitro and in vivo in animal models of ocular neovascularisation, together with promising synergistic effects with existing VEGF inhibitors.[3],[4] In this work, the phytochemistry of three species of Rhodocodon (Scilloideaea subfamily of the Asparagaceae family), endemic to Madagascar, R. cryptodus, R. rotundus and R. cyathiformis, was investigated. 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, together with three cinnamic acid derivatives 3-5, four bufadienolides 6-9 and a coumarin 10 [ Fig. 1 ]. The antiangiogenic activity of the two homoisoflavonoids was tested against human retinal microvascular endothelial cells (HRECs), giving excellent GI50 results of 0.13 µM and 0.49 µM respectively. Moreover, compound 2 showed a 100-fold specificity for HRECs over other tested cell lines. Its high antiangiogenic activity and promising specificity make compound 2 a suitable candidate in the development of new treatments against ocular neovascularization.

Zoom Image
Fig. 1 Compounds isolated from R. cryptodus, R. rotundus and R. cyathiformis.
 

  • References

  • 1 Penn JS, Madan A, Caldwell RB, Bartoli M, Caldwell RW, Hartnett ME. Vascular endothelial growth factor in eye disease. Prog Retin Eye Res 2008; 27: 331-371.
    CrossrefPubMedGoogle Scholar
  • 2 Lux A, Llacer H, Heussen FM, Joussen AM. Non-responders to bevacizumab (Avastin) therapy of choroidal neovascular lesions. Br J Ophthalmol 2007; 91: 1318-1322
    CrossrefPubMedGoogle Scholar
  • 3 Schwikkard S, Whitmore H, Sishtla K, Sulaiman RS, Shetty T, Basavarajappa HD. et al. The antiangiogenic activity of naturally occurring and synthetic homoisoflavonoids from the hyacinthaceae (sensu APGII). J Nat Prod 2019; ; doi: DOI: 10.1021/acs.jnatprod.8b00989.
    CrossrefPubMedGoogle Scholar
  • 4 Sulaiman RS, Merrigan S, Quigley J, Qi X, Lee B, Boulton ME. et al. A novel small molecule ameliorates ocular neovascularisation and synergises with anti-VEGF therapy. Sci Rep 2016; 6: 25509
    CrossrefPubMedGoogle Scholar