In an attempt to obtain inhibitors of hyaluronic acid (HA) binding to its receptor, CD44, we established an efficient assay method to detect and quantify binding using fluorescein-labeled HA and HEK293 cells stably expressing CD44. As a result of the screening of culture broths of microorganisms, we found fungus strain Gloeoporus dichrous SANK 30502 produced inhibitory activity in this new assay. Five compounds, F-16438 A, B, E, F and G, were isolated from the fermentation broths, and their IC50 values were determined to be 10.3, 13.5, 27.3, 12.0 and 13.0 microM, respectively. F-16438 A, B, E, F and G are the first reported inhibitors of binding HA to CD44. F-16438 A, B, E and F have novel structures.
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