Short Lecture "Synthetic homoisoflavonoids for the treatment of choroidal neovascularisation"

The process of choroidal neovascularisation is associated with debilitating ocular diseases such as age- related macular degeneration, retinopathy of prematurity and proliferative diabetic retinopathy, the former of which is the most prevalent cause of blindness in the ageing population. The existing treatments for these diseases consist of monoclonal antibodies and decoy receptors that bind to vascular endothelial growth factor to prevent excessive angiogenesis of the ocular vasculature. These high molecular weight biologics must be introduced to the patient via intravitreal injection, a painful process which is associated with a range of undesirable side effects and resistance issues. Homoisoflavonoids are a class of naturally occurring compounds that have been isolated from plant families such as Asparagaceae, species of which have been long used by traditional healers in Eastern and Southern Africa. Both synthetic and isolated homoisoflavonoid compounds have been shown previously to possess antiproliferative and antiangiogenic activities against human retinal endothelial cells (HRECs). This presents an exciting opportunity for the development of an alternative small molecule biologic to treat diseases associated with choroidal neovascularisation, which may provide a less invasive route of administration. Though homoisoflavonoid compounds may be found in nature, synthetic derivatives with a range of non-naturally derived heteroatoms and functional groups may provide exciting biological activity. We describe our syntheses of derivatised (E)-3-benzylidene-4-chromanones and 3- benzylchromanes ([Fig. 1]). Initial screening showed promising results, with two synthetic homoisoflavonoids exhibiting growth inhibitory concentrations of 4.9 µM and 12 µM against the proliferation of HRECs.

Fig. 1 Examples of synthetic (E)-3-benzylidene-4-chromanone homoisoflavonoids.

Publication History

Article published online:
16 November 2023