Novel protostane-type triterpenoids with inhibitory human carboxylesterase 2 activities
Novel protostane-type triterpenoids with inhibitory human carboxylesterase 2 activities
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DOI：
10.1039/c7ra04841f
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发表时间：
2017-05
期刊：
影响因子：
3.9
通讯作者：
Zhi-jie Zhang;Xiaokui Huo;Xiangge Tian;Lei Feng;Jing Ning;Xinyu Zhao;Chengpeng Sun;Chao Wang
中科院分区：
文献类型：
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作者：
Zhi-jie Zhang;Xiaokui Huo;Xiangge Tian;Lei Feng;Jing Ning;Xinyu Zhao;Chengpeng Sun;Chao Wang
泽泻的根茎在中国和其他亚洲国家作为一种有效的草药已经使用了几个世纪。通过对东洋蓟的植物化学研究，以及Cunninghamella elagans AS 3.2028和青霉janthinellum AS 3.510对东洋蓟中两种主要的三萜醇A（11）和b23 -acetate（13）的生物转化，分离出10种新的原烷型三萜（1 - 5和18-22），包括一种新的26-非原烷(1)和一种罕见的17-非原烷(2)，以及12种已知的类似物。通过一维、二维核磁共振和HRESIMS光谱分析确定了它们的结构。测定了所有化合物对人羧酸酯酶2 （HCE-2）的抑制活性。化合物1、3 ~ 9、12、14 ~ 16、19、20对HCE-2具有显著的抑制活性，IC50值为0.51±0.09 ~ 9.45±0.73 μM。建立了化合物5对HCE-2的抑制动力学，测定了其Ki值为0.57 μM。采用分子对接的方法研究了化合物5与HCE-2的相互作用。
The rhizomes of Alisma orientalis have been used for centuries in China and other Asian countries as an effective herbal remedy. The phytochemical investigation of A. orientalis and biotransformation of two major triterpenoids alisols A (11) and B 23-acetate (13) by Cunninghamella elagans AS 3.2028 and Penicillium janthinellum AS 3.510 have led to the isolation of ten new protostane-type triterpenoids (1–5 and 18–22), including one novel 26-nor-protostane (1) and one unusual 17-nor-protostane (2), together with twelve known analogues. Their structures were determined by 1D and 2D NMR, and HRESIMS spectroscopic analyses. All the isolated compounds were assayed for their inhibitory activities against human carboxylesterase 2 (HCE-2). Compounds 1, 3–9, 12, 14–16, 19, and 20 showed significant inhibitory activities on HCE-2 with IC50 values from 0.51 ± 0.09 μM to 9.45 ± 0.73 μM. The inhibition kinetics of compound 5 toward HCE-2 were established, and its Ki value was determined as 0.57 μM. The interaction of compound 5 with HCE-2 was investigated using molecular docking.