Sulphur Analogues of Homoisoflavonoids as Potential Treatments for Neovascular Eye Diseases

TL;DR

Scientists developed new sulfur-based compounds that may help treat eye diseases by reducing harmful blood vessel growth and inflammation.

Contribution

The paper introduces new sulfur analogues of homoisoflavonoids with antiangiogenic and anti-inflammatory properties for potential use in treating neovascular eye diseases.

Findings

Compound 10 showed strong anti-proliferation against retinal endothelial cells with minimal toxicity to retinal pigment epithelial cells.

Compound 10 significantly reduced angiogenesis in a Matrigel tube formation assay at low concentrations.

Compound 7 exhibited the highest COX-II inhibition among the tested analogues.

Abstract

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.

Neovascular eye diseases are characterised by the abnormal growth of often fragile blood vessels in the eye. Treatment focuses on reducing angiogenesis as well as reducing oxidative stress induced inflammation, a key underlying cause. Synthetic sulphur analogues of naturally occurring homoisoflavonoids, synthesised in three steps, have shown promise as antiangiogenic and anti‐inflammatory agents in vitro.© 2026 WILEY‐VCH GmbH

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