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 71:209-218, 2010. (C) 2010 Wiley-Liss, Inc.