State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, People's Republic of China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Zhangjiang Hi-Tech Park, Shanghai 201203, People's Republic of China; Shanghai Collaborative Innovation Center for Biomanufacturing Technology, 130 Meilong Road, Shanghai 200237, People's Republic of China; Biology Department, College of Life and Environment Science, Shanghai Normal University,100 Guilin Road, Shanghai 200234, People's Republic of China.
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Zhangjiang Hi-Tech Park, Shanghai 201203, People's Republic of China.
Bioorg Chem. 2020 Mar;96:103636. doi: 10.1016/j.bioorg.2020.103636. Epub 2020 Feb 8.
Three new nardosinane-type sesquiterpenoids linardosinenes A-C (1-3) and four new neolemnane-type sesquiterpenoids lineolemnenes A-D (4-7), together with the related known compound 4-acetoxy-2,8-neolemnadien-5-one (8), were isolated from the Xisha soft coral Litophyton nigrum. The structures of these new compounds were elucidated by comprehensive analyses of spectroscopic data, in association withmodified Mosher's method and ECD calculations for configurational assignments and the absolute configuration of8was determined by X-ray diffraction analysis for the first time. Structurally uncommon nornardosinane and seconeolemnane skeletons for compounds 1 and 7, respectively, are rare carbon frameworks in naturally occurring sesquiterpenoids. The absolute configurations of 1, 7, and 8 were determined by modified Mosher's method, TDDFT ECD approach, and X-ray diffraction analysis, respectively. This is the first chemical study of L. nigrum and the first report of nornardosinane, seconeolemnane and related sesquiterpenoids from the genus Litophyton. The isolates 1-7 were evaluated for their cytotoxicity against THP-1, SNU-398, HT-29, Capan-1 and A549 cell lines and inhibitory activities against PTP1B, BRD4, HDAC1 and HDAC6 protein kinases. The results indicated that compounds 2-5 inhibited proliferation of human cancer cells. However, none of them were potent inhibitors of protein kinases.
从西沙软珊瑚 Litophyton nigrum 中分离得到了三种新的纳多赛烷型倍半萜类化合物 linardosinenes A-C（1-3）和四种新的新罗汉烷型倍半萜类化合物 lineolemnenes A-D（4-7），以及相关的已知化合物 4-乙酰氧基-2,8-新罗汉二烯-5-酮（8）。这些新化合物的结构通过综合分析光谱数据，结合改良的 Mosher 法和 ECD 计算确定构型分配以及 8 的绝对构型首次通过 X 射线衍射分析确定。化合物 1 和 7 分别具有结构上不常见的诺纳多赛烷和 seconeolemnane 骨架，它们是天然存在的倍半萜中罕见的碳骨架。通过改良的 Mosher 法、TDDFT ECD 方法和 X 射线衍射分析分别确定了 1、7 和 8 的绝对构型。这是对 L. nigrum 的首次化学研究，也是首次报道来自 Litophyton 属的诺纳多赛烷、seconeolemnane 和相关倍半萜类化合物。对 1-7 进行了细胞毒性评估，检测其对 THP-1、SNU-398、HT-29、Capan-1 和 A549 细胞系的抑制作用，以及对 PTP1B、BRD4、HDAC1 和 HDAC6 蛋白激酶的抑制活性。结果表明，化合物 2-5 抑制了人类癌细胞的增殖。然而，它们都不是蛋白激酶的有效抑制剂。
