A Novel Bone Resorption Inhibitor, A-75943 Isolated from Streptomyces sp. SANK 61296

Abstract

A novel bone resorption inhibitor, A-75943, was isolated from Streptomyces sp. SANK 61296. Its structure was determined to be (1″S, 2′R, 3″S, 4S′, 5″S)-2-[3″, 5″-dimethyl-2″-oxocyclohexan-1″-yl)-6′-oxotetrahydropyran-4′-yl]acetamide by spectral analyses and chemical conversion of cycloheximide. A-75943 inhibited bone resorption in vitro in a concentration-dependent manner with an IC₅₀ of 0.35 μM, and also displayed an inhibitory effect on bone resorption in thyroid and parathyroid-extracted rats.