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Hiles, Jacob D., Deri, Ola, Sishtla, Kamakshi, Bear, Joseph C., Cockcroft, Jeremy K., Opara, Elizabeth, Al‐Kinani, Ali A., Alany, Raid G., Corson, Timothy W. and Schwikkard, Sianne L. (2026) Sulphur analogues of homoisoflavonoids as potential treatments for neovascular eye diseases. ChemMedChem, 21 (2): e202500824. pp. 1-11. ISSN 1860-7187
Treatment of neovascular eye diseases like age‐related macular degeneration require a compound that is not toxic to ocular cells, that can reduce inflammation and inhibit angiogenesis. Homoisoflavonoids, naturally occurring compounds isolated primarily from the Hyacinthaceae sub‐family of plants, have shown promise as anti‐inflammatories and inhibitors of angiogenesis. A series of sulphur analogues, (3‐benzylidene thiochroman‐4‐ones), were synthesised via a three‐step procedure. These compounds were evaluated for selectivity towards endothelial cells over non‐endothelial cells and their ability to inhibit COX‐II over COX‐I.Their potential anti‐angiogenic activity was assessed using the Matrigel tube formation assay. (3Z)‐3‐[(3‐bromophenyl)methylidene]‐6‐methoxy‐2,3‐dihydro‐4H‐1‐benzothiopyran‐4‐one (10) was most active with respect to anti‐proliferation against human retinal endothelial cells (HREC cells) (GI50 3.07 μM). All demonstrated selectivity with all GI50 values against retinal pigment epithelial cell line ARPE‐19 >100 µM, with the exception of (3Z)‐6‐bromo‐3‐[(4‐nitrophenyl)methylidene]‐2,3‐dihydro‐4H‐1‐benzothiopyran‐4‐one (12), which was not toxic to either. (3Z)‐3‐[(3‐bromophenyl)methylidene]‐6‐methoxy‐2,3‐dihydro‐4H‐1‐benzothiopyran‐4‐one (10) showed significant reduction in angiogenesis properties in a Matrigel‐based tube formation assay (38.79%, 5 µM, 56.41%, 10 µM). (3Z)‐6‐bromo‐3‐[(3‐bromophenyl)methylidene]‐2,3‐dihydro‐4H‐1‐benzothiopyran‐4‐one (7) was found to be the most active against COX‐II with inhibition of 22.7 % (4.35 nM). The 3‐benzylidene thiochroman‐4‐ones show promise as antiangiogenic agents, but limited selectivity to COX‐II over COX‐I.
Available under License Creative Commons Attribution 4.0.
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