Wu Jianzhang, Xi Yiyuan, Li Ge, Zheng Yuantie, Wang Zhongle, Wang Jingsong, Fang Chengyan, Sun Zhongmin, Hu Linya, Jiang Wei, Dai Lishang, Dong Jianyong, Qiu Peihong, Zhao Min, Yan Pengcheng
School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, People's Republic of China.
Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, People's Republic of China.
J Nat Prod. 2021 Apr 23;84(4):1306-1315. doi: 10.1021/acs.jnatprod.1c00027. Epub 2021 Mar 16.
Five new diterpenes, including four new hydroazulenes, (8,11)-8,11-diacetoxypachydictyol A (), (8*,11*)-6--acetyl-8-acetoxy-11-hydroxypachydictyol A (), (8*,11*)-8-acetoxy-11-hydroxypachydictyol A (), and (8*,11*)-6--acetyl-8,11-dihydroxypachydictyol A (), and a secohydroazulene derivative, named 7-7,8-seco-7,11-didehydro-8- acetoxypachydictyol A (), were isolated from a South China Sea collection of a sp. nov. brown alga, together with five known analogues (-). Structure elucidation was achieved by extensive spectroscopic analysis and comparison with reported data. All compounds showed potent antioxidant effects against HO-induced oxidative damage in neuron-like PC12 cells at a low concentration of 2 μM. The antioxidant property of dictyol C () was associated with activation of the Nrf2/ARE signaling pathway; it also showed neuroprotective effects against cerebral ischemia-reperfusion injury (CIRI) in a rat model of transient middle cerebral artery occlusion. As such, hydroazulene diterpenes could serve as lead structures for the development of novel neuroprotective agents against CIRI.
从中国南海采集的一种新的褐藻（新物种）中分离出五种新的二萜类化合物，包括四种新的氢化薁类化合物，（8,11）-8,11-二乙酰氧基厚叶藻醇A（）、（8*,11*）-6-乙酰基-8-乙酰氧基-11-羟基厚叶藻醇A（）、（8*,11*）-8-乙酰氧基-11-羟基厚叶藻醇A（）和（8*,11*）-6-乙酰基-8,11-二羟基厚叶藻醇A（），以及一种裂环氢化薁衍生物，命名为7-7,8-裂环-7,11-二脱氢-8-乙酰氧基厚叶藻醇A（），同时还分离出五种已知类似物（-）。通过广泛的光谱分析并与已报道的数据进行比较来确定结构。所有化合物在2μM的低浓度下对HO诱导的神经样PC12细胞氧化损伤均表现出强大的抗氧化作用。厚叶藻醇C（）的抗氧化特性与Nrf2/ARE信号通路的激活有关；它在短暂性大脑中动脉闭塞大鼠模型中也对脑缺血再灌注损伤（CIRI）表现出神经保护作用。因此，氢化薁二萜类化合物可作为开发新型抗CIRI神经保护剂的先导结构。
