Identification of Ingol and Rhamnofolane Diterpenoids from Euphorbia resinifera and Their Abilities to Induce Lysosomal Biosynthesis
Identification of Ingol and Rhamnofolane Diterpenoids from Euphorbia resinifera and Their Abilities to Induce Lysosomal Biosynthesis
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大戟中 Ingol 和鼠李叶烷二萜的鉴定及其诱导溶酶体生物合成的能力
DOI：
10.1021/acs.jnatprod.7b00981
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发表时间：
2018-05-01
影响因子：
5.1
通讯作者：
Li, Shun-Lin
中科院分区：
文献类型：
--
作者：
Zhao, Ning-Dong;Ding, Xiao;Li, Shun-Lin
大戟属植物化学研究得到18种结构多样的二萜类化合物，包括14种新的ingol型二萜，大戟属a - n(1-14)，一种新的鼠李糖烷二萜，大戟属0 （Is）和3种已知的类似物（16-18）。利用二维核磁共振波谱和NOE实验推导了这些化合物的结构。化合物1的结构通过单晶x射线晶体学得到了证实。通过LysoTracker Red染色评价化合物促进溶酶体生物合成的能力。10个活性化合物中，化合物2、4和18表现出显著的免疫荧光强度，其LysoTracker染色强度分别比对照高155.9%、143.5%和140.7%。一系列溶酶体基因也被发现被这些化合物上调，这进一步证实了它们诱导溶酶体生物合成的能力，并表明这些二萜类化合物有潜力作为开发治疗溶酶体相关疾病的药物的先导化合物。
The phytochemical study of Euphorbia resinifera afforded 18 structurally diverse diterpenoids, including 14 new ingol-type diterpenoids, euphorblins A-N (1-14), a new rhamnofolane diterpenoid, euphorblin 0 (Is), and three known analogues (16-18). The structures of these compounds were deduced using 2D NMR spectroscopy and NOE experiments. The structure of compound 1 was confirmed by single-crystal X-ray crystallography. The abilities of the compounds to enhance lysosomal biosynthesis were evaluated through LysoTracker Red staining. Among the 10 active compounds, compounds 2, 4, and 18 showed remarkable immunofluorescence strength, and their LysoTracker staining intensities were 155.9%, 143.5%, and 140.7%, respectively, greater than that of the control. A series of lysosomal genes were also found to be upregulated by these compounds, which further confirms their ability to induce lysosome biosynthesis and suggests that these diterpenoids have potential as lead compounds for the development of drugs for the treatment of lysosome-related diseases.