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Synthesis and identification of homoisoflavonoids and lignans for the treatment of wet active age-related macular degeneration based on their anti-vascular endothelial growth factor and anti-inflammatory activities


Faculty of Science, Engineering and Computing

About the Project

Age-related macular degeneration is reported to be the most common cause of visual impairment, and its certification, in the developed world. This condition is classified based on early and late onset of the disease. Regarding the latter, there are three forms – wet inactive, wet active and dry. In the wet active form, excessive blood vessel formation (neovascularization) in the eye is implicated. In addition to the action of increased vascular endothelial growth factor (VEGF), there is growing evidence that chronic inflammation has a major role to play in the formation and progression of the vascularization that occurs. The need for small molecule antiangiogenic drugs to supplement existing biologics, which target VEGF, in the treatment of this condition, has been identified. Homoisoflavonoids have been previously shown to have potent anti-proliferative activities on endothelial cells over other cell types. Moreover, they demonstrated a strong antiangiogenic potential in vitro and in vivo in animal models of ocular neovascularization. In addition, homoisoflavonoids and lignans have shown selective COX-II inhibitory activity, and it is well established that COX-II is a key mediator of chronic inflammation
Recent research recognises the benefit of developing agents/compounds that possess anti-inflammatory and anti-VEGF activity as they may provide a more effective and novel strategy for treating AMD. Therefore, the project will involve the design and stereospecific synthesis of homoisoflavonoids and lignans for analysis as both anti-angiogenic and anti-inflammatory (specifically selective COX-II inhibitors) agents. The compounds will be analysed for COX-II inhibitory and other anti-inflammatory activity and cytotoxicity at Kingston University and for anti-angiogenic activity at the Glick Eye Institute in Indiana. The project will provide a diverse training experience for the student including both synthetic organic chemistry, tissue culture and the carrying out of key biological assays.


Funding Notes

No funding is avaiable

References

Sianne L. Schwikkard1,2, Hannah Whitmore2, Timothy W. Corson3, Kamakshi Sishtla3, Moses K. Langat2,4, Mark Carew1 and Dulcie A. Mulholland. (2018) Antiangiogenic Activity and Cytotoxicity of Triterpenoids and Homoisoflavonoids from Massonia pustulata and Massonia bifolia Planta Medica, 84, 638-644

Schwikkard, S L; Alqahtani, A; Knirsch, W; Wetschnig, W, Opara, E. I, Jaksevicius, A, Langat, M K, Andriantiana, J and Mulholland, D A. (2017) Phytochemical Investigations of Three Rhodocodon (Hyacinthaceae Sensu APG II) Species Journal of Natural Products, 80 (1), 30-37

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