New biological investigations on 3‐bromophenyl 6‐acetoxymethyl‐2‐oxo‐2H‐1‐benzopyran‐3‐carboxylate as anti‐angiogenic agent

The development of blood vessels inside tumors is required to provide the nutrients and oxygen needed for tumor growth and to allow the spread of cancer cells at a distance to form metastasis. Angiogenesis is also implicated in ocular diseases like age‐related macular degeneration. The present work describes the potential anti‐angiogenic properties of a coumarinic derivative, 3‐bromophenyl 6‐acetoxymethyl‐2‐oxo‐2H‐1‐benzopyran‐3‐carboxylate (IK9), previously described as a potent inhibitor of HT 1080 fibrosarcoma cell invasion in vitro and tumor growth in vivo. In vivo, ex vivo, and in vitro models were used to delineate the anti‐angiogenic properties of IK9. The anti‐angiogenic effect of IK9 was demonstrated in vivo in a choroidal neovascularization mice model and additionally ex vivo in a rat aortic ring assay where it was more active than the known matrix metalloproteinase inhibitor Ro 28‐2653. IK9 did not affect apoptosis, proliferation, or endothelial cell invasiveness in vitro. These findings suggest a complex mechanism of action of the compound via direct or indirect effects on endothelial cell properties. This study identifies IK9 as a new potent inhibitor of angiogenesis and suggests its potential use as a therapeutic agent. Drug Dev Res 71, 2010. © 2010 Wiley‐Liss, Inc.