Research Center for Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, People's Republic of China.
Research Center for Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, People's Republic of China; Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, People's Republic of China.
Bioorg Chem. 2020 Jan;94:103453. doi: 10.1016/j.bioorg.2019.103453. Epub 2019 Nov 23.
Compounds 1-11 were isolated from the aerial parts of Flueggea acicularis Croizz Webster, including three new rearranged clesistanthane diterpenoids fluacinoids A-C (1-3) and five new norditerpenoid fluacinoids D-H (4-8). The new compounds were identified from spectroscopic data combined with single crystal X-ray diffraction analysis, modified Mosher's methods, and ECD data analyses. All the isolated compounds were evaluated for their activities on RANKL-induced osteoclastogenesis in bone marrow monocytes (BMMs). Compound 6 showed the most potent inhibition against osteoclast differentiation (IC, 0.7 μM) and decreased the expression level of osteoclast-related genes. Moreover, compound 6 prompted the apoptosis of osteoclasts. Compound 6 also suppressed RANKL-induced NF-κB activation. This study reveals that norditerpenoids may be resource for anti-osteoporosis agents.
化合物 1-11 从 Flueggea acicularis Croizz Webster 的地上部分中分离得到，包括三个新的重排 clesistanthane 二萜类 fluacinoids A-C (1-3) 和五个新的 norditerpenoid fluacinoids D-H (4-8)。新化合物通过光谱数据与单晶 X 射线衍射分析、改进的 Mosher 方法和 ECD 数据分析相结合进行鉴定。所有分离得到的化合物都进行了 RANKL 诱导的破骨细胞分化在骨髓单核细胞 (BMMs) 中的活性评价。化合物 6 对破骨细胞分化的抑制作用最强 (IC，0.7 μM)，并降低了破骨细胞相关基因的表达水平。此外，化合物 6 促使破骨细胞凋亡。化合物 6 还抑制了 RANKL 诱导的 NF-κB 激活。本研究表明， norditerpenoids 可能是抗骨质疏松药物的资源。
