A natural inhibitor from Alisma orientale against human carboxylesterase 2: Kinetics, circular dichroism spectroscopic analysis, and docking simulation
A natural inhibitor from Alisma orientale against human carboxylesterase 2: Kinetics, circular dichroism spectroscopic analysis, and docking simulation
复制标题
泽泻对人羧酸酯酶 2 的天然抑制剂：动力学、圆二色性光谱分析和对接模拟
DOI：
10.1016/j.ijbiomac.2019.04.099
复制
发表时间：
2019
影响因子：
8.2
通讯作者：
Zhang Hou Li
中科院分区：
文献类型：
--
作者：
Yi Jing;Bai Rong;An Yue;Liu Tian Tian;Liang Jia Hao;Tian Xiang Ge;Huo Xiao Kui;Feng Lei;Ning Jing;Sun Cheng Peng;Ma Xiao Chi;Zhang Hou Li
作为从中药中寻找天然的人CES-2抑制剂的一部分，我们发现泽泻提取物在体外对人CES-2有明显的抑制作用。分离得到一个新的原斯坦型三萜类泽泻素I(1)。根据HRESIMS、一维和二维核磁共振波谱确定了其结构。人CES2介导的DDAB水解法测得泽泻素I(1)对人CES2有明显的抑制作用，IC50值为1.31 ± 0.09 μM。根据其抑制动力学结果，化合物1为非竞争性抑制物，其KI为3.65 μM，其抑制作用在活细胞水平上得到直观证实。通过圆二色谱(CD)和分子对接分析了化合物1与人CES2的潜在相互作用机理。
As a part of our searching for natural human carboxylesterase 2 (human CES 2) inhibitors from traditional Chinese medicine, we found that the extract ofAlismaorientalesignificantly inhibited human CES 2in vitro. The investigation onA.orientaleled to the isolation of a new protostane-type triterpenoid alismanin I (1). Its structure was determined according to HRESIMS, 1D and 2D NMR spectra. Alismanin I (1) displayed significantly inhibitory activity against human CES 2 with IC50value of 1.31 ± 0.09 μM assayed by human CES 2-mediated DDAB hydrolysis. According to its inhibition kinetic result, compound1was a noncompetitive type inhibitor, and its Ki was 3.65 μM. Its inhibitory effect was confirmed in living cell level through a visual manner. The potential interaction mechanism of compound1with human CES 2 was also analyzed by circular dichroism (CD) spectrum and molecular docking.