Pestanoid A, a Rearranged Pimarane Diterpenoid Osteoclastogenesis Inhibitor from a Marine Mesophotic Zone Chalinidae Sponge-Associated Fungus, Pestalotiopsis sp. NBUF145.

One novel rearranged pimarane diterpenoid, pestanoid A ( 1 ), and two reported molecules, nodulisporenones A ( 2 ) and B ( 3 ), were discovered from Pestalotiopsis sp. NBUF145 fungus associated with a 62 m deep mesophotic ("twilight") zone Chalinidae sponge. The structures of 1 - 3 were identified by spectrometry, spectroscopy, quantum-chemical calculations, and X-ray crystallography. Compounds 1 and 2 inhibited bone marrow monocyte osteoclastogenesis in vitro with the IC 50 values 4.2 ± 0.2 μM and 3.0 ± 0.4 μM, respectively, without observed cytotoxicity. Both 1 and 2 suppressed the receptor activator of NF-kB ligand-induced MAPK and NF-κB signaling by inhibiting the phosphorylation of ERK1/2-JNK1/2-p38 MAPKs and NF-κB nuclear translocation.