The structure of wondonin marine natural products was renovated to attain new drug-like scaffolds. Wondonins have novel antiangiogenic properties without overt cytotoxicity. However, the chemical instability and synthetic complexity of wondonins have hindered their development as a new type of antiangiogenesis agent. Using a structure-based bioisosterism, the benzodioxole moiety was changed to benzothiazole, and the imidazole moiety was replaced by 1,2,3-triazole. Our efforts resulted in a new scaffold with enhanced antiangiogenic activity and minimized cytotoxicity. One compound with this scaffold effectively inhibited hyaloid vessel formation in diabetic retinopathy mimic zebrafish model. The biological findings together suggested the potential of the scaffold as a lead structure for development of antiangiogenic drugs with novel functions and as a probe to elucidate new biological mechanisms associated with angiogenesis.

中文翻译：

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Wondonin天然产物的靶向化学转化发现了新的血管生成抑制剂支架。

对馄饨素海洋天然产物的结构进行了翻新，以获得新的药物样支架。Wondonins具有新颖的抗血管生成特性，没有明显的细胞毒性。然而，馄饨蛋白的化学不稳定性和合成复杂性阻碍了它们作为新型抗血管生成剂的发展。使用基于结构的生物立体异构，将苯并二恶唑部分更改为苯并噻唑，并将咪唑部分替换为1,2,3-三唑。我们的努力导致了一种具有增强的抗血管生成活性和最小化细胞毒性的新型支架。具有这种支架的一种化合物在糖尿病性视网膜病模拟斑马鱼模型中有效抑制玻璃样血管的形成。