Montagnulans A–D with Anti-Osteoclastogenic Activity from the Marine Fungus Montagnula sp. GXIMD 02514

Four novel tetramic acid compounds, montagnulans A-D (<b>1</b>-<b>4</b>), were obtained from the Beibu Gulf coral-associated fungus <i>Montagnula</i> sp. GXIMD 02514. Their structures were determined by comprehensive physicochemical and spectroscopic data interpretation. The absolute configurations were accomplished by ECD calculations. Structurally, compounds <b>1</b>-<b>4</b> were rare leucine-derived tetramic acids bearing an ethyl (<b>1</b>-<b>3</b>) or hexylenic alcohol (<b>4</b>) side chain and a pyranone ring at C-3 of the 2,4-pyrrolidinedione core. Compound <b>1</b> exhibited inhibition of lipopolysaccharide (LPS)-induced NF-<i>κ</i>B in RAW 264.7 macrophages at 20 μM, which further inhibited RANKL-induced osteoclast differentiation without cytotoxicity in bone marrow macrophages cells (BMMs). This is the first report of osteoclastogenesis inhibitions for tetramic acids, which sheds light on their development as potential osteoclast differentiation inhibitors.