Identification of Antiangiogenic Potential and Cellular Mechanisms of Napyradiomycin A1 Isolated from the Marine-Derived <i>Streptomyces</i> sp. YP127

Angiogenesis is the process of new blood vessel formation. Excessive angiogenesis is a critical factor in the progression of cancer, macular degeneration, and other chronic inflammatory diseases. When investigating the effects of crude extracts of cultured marine microorganisms, an extract of the cultured <i>Streptomyces</i> sp. YP127 strain was found to inhibit human umbilical vein endothelial cell (HUVEC) tube formation. Bioassay-guided fractionation and spectroscopic data analyses led to the identification of napyradiomycin A1 (<b>1</b>) as an antiangiogenic component of the extract. Compound <b>1</b> inhibited HUVEC tube formation in a concentration-dependent manner. It inhibited endothelial cell proliferation but did not affect human dermal fibroblast proliferation. Compound <b>1</b> also suppressed migration and invasion of vascular endothelial cells. In addition, compound <b>1</b> suppressed vascular endothelial cadherin expression and increased the permeability of the endothelial cell membrane. These results suggested that compound <b>1</b> modulates cell permeability and inhibits the angiogenesis of endothelial cells