Natural and Synthetic Homoisoflavonoids and Related Compounds for the Treatment of Macular Degeneration

The inhibition of angiogenesis is a drug target with widespread application. Macular conditions affect around 1.5 million people in the UK, with most of them suffering from age-related macular degeneration. AMD is the biggest cause of sight loss in the UK, affecting about 600 000 people [1]. Wet age-related macular degeneration it is characterized by extensive neovascularisation of the retina. Current treatments include the use of anti-VEGF agents such as Bevacizumab (Avastin) and Ranibizumab (Lucentis). Due to the cost of these treatments and the variable outcomes, the possibility of a small molecule treatment is very attractive. Homoisoflavonoids are C-16 natural products isolated primarily from the Asparagaceae family ([Fig. 1]). These compounds have shown promising activity in vitro and in some initial in vivo analyses. A wide range of homoisoflavonoids, both extracted from natural sources as well as of synthetic origin have been screened for selectivity towards human retinal microvascular endothelial (HREC) cells, as well as being assessed for their ability to inhibit tube formation using a Matrigel assay. The work has highlighted some key structural features that are important for activity and selectivity. Synthetic methodology has been developed and optimised to allow for the production of a range of structurally diverse homoisoflavonoids showing good activity and promise for further development as therapeutic agents.

Fig. 1 Synthetic homoisoflavonoid GI50 (HREC) 0.035 µM.

Publication History

Article published online:
12 December 2022

• Reference

• 1 The Macular Society UK. https://www.macularsociety.org