Peniditerpenoids A and B: Oxidized Indole Diterpenoids with Osteoclast Differentiation Inhibitory Activity from a Mangrove-Sediment-Derived Penicillium sp.

作者：Jian Cai, Min Li, Chunmei Chen, Bin Yang, Chenghai Gao, Yonghong Liu, Xiaowei Luo, Yanhui Tan, Xuefeng Zhou · 发表于：Journal of Natural Products · 年份：2024 · DOI：10.1021/acs.jnatprod.4c00116 · 被引用次数：18 · 研究领域：Microbial Natural Products and Biosynthesis、Natural product bioactivities and synthesis、Marine Sponges and Natural Products

An unprecedented di- seco -indole diterpenoid, peniditerpenoid A ( 1 ), and a rare N -oxide-containing indole diterpenoid derivative, peniditerpenoid B ( 2 ), together with three known ones ( 3 – 5 ), were obtained from the mangrove-sediment-derived fungus Penicillium sp. SCSIO 41411. Their structures were determined by the analysis of spectroscopic data, quantum chemical calculations, and X-ray diffraction analyses. Peniditerpenoid A ( 1 ) inhibited lipopolysaccharide-induced NF-κB with an IC 50 value of 11 μM and further effectively prevented RANKL-induced osteoclast differentiation in bone marrow macrophages. In vitro studies demonstrated that 1 exerted significant inhibition of NF-κB activation in the classical pathway by preventing TAK1 activation, IκBα phosphorylation, and p65 translocation. Furthermore, 1 effectively reduced the level of NFATc1 activation, resulting in the attenuation of osteoclast differentiation. Our findings suggest that 1 holds promise as an inhibitor with significant potential for the treatment of diseases related to osteoporosis.