钩藤对人羧酸酯酶2抑制作用的化学成分:动力学和相互作用机制与对接模拟相结合。

PubMed ID
G H
发表日期 2018年Dec月

原始出处 植物医学:国际植物治疗与植物药理学杂志
Phytomedicine : international journal of phytotherapy and phytopharmacology
作者 Wang  Ya-Li  Dong  Pei-Pei  Liang  Jia-Hao  Li  Ning  Sun  Cheng-Peng  Tian  Xiang-Ge  Huo  Xiao-Kui  Zhang  Bao-Jing  Ma  Xiao-Chi  Lv  Chuan-Zhu 

文献标题 钩藤对人羧酸酯酶2抑制作用的化学成分:动力学和相互作用机制与对接模拟相结合。
Phytochemical constituents from Uncaria rhynchophylla in human carboxylesterase 2 inhibition: Kinetics and interaction mechanism merged with docking simulations.
Phytochemical constituents from Uncaria rhynchophylla in human carboxylesterase 2 inhibition: Kinetics and interaction mechanism merged with docking simulations.

文献摘要 BACKGROUND

羧酸酯酶(carboxyasterases,CEs)属于丝氨酸水解酶家族,主要通过丝氨酸-谷氨酸(Ser-His-Glu)水解含有羧酸酯和酰胺官能团的化学物质。钩藤。前哈维尔。是我国治疗高热、癫痫、子痫前期和高血压的著名中药。

HYPOTHESIS/PURPOSE

从钩藤中寻找潜在的天然人羧酸酯酶2(hce2)抑制剂。

METHODS

采用硅胶柱层析和制备高效液相色谱法从钩藤钩子中分离得到化合物。利用HRESIMS、1D和2dnmr谱对其结构进行了表征。用荧光探针测定了它们对hce2的抑制活性和抑制动力学,并通过分子对接研究了它们的作用机制。

RESULTS

从钩藤中分离得到23个化合物,包括一个新的酚酸钩藤碱a(1)、8个已知的三萜(2-9)和10个已知的芳香族衍生物(10、13-16和19-23)。化合物1-5、7、9、15对HCE2具有明显的抑制活性,IC50值为4.01±±±±±±±±±±±±±±±0.21µM,其抑制动力学分析结果表明:化合物1、5、9、15为非竞争性;化合物3、4为混合型,化合物2、7为非竞争性。分子对接研究表明化合物1-5、7、9和15对hce2的抑制机制。

CONCLUSION

我们目前的发现突出了钩藤中潜在的天然hCE 2抑制剂。


BACKGROUND

Carboxylesterases (CEs) belong to the serine hydrolase family, and are in charge of hydrolyzing chemicals with carboxylic acid ester and amide functional groups via Ser-His-Glu. Uncaria rhynchophylla (Miq.) Miq. ex Havil. is a famous traditional Chinese medicine used in managing hyperpyrexia, epilepsy, preeclampsia, and hypertension in China.

HYPOTHESIS/PURPOSE

To discover the potential natural human carboxylesterase 2 (hCE 2) inhibitors from U. rhynchophylla.

METHODS

Compounds were obtained from the hooks of U. rhynchophylla by silica gel and preparative HPLC. Their structures were elucidated by using HRESIMS, 1D and 2D NMR spectra. Their inhibitory activeties and inhibition kinetics against hCE 2 were assayed by the fluorescent probe, and potential mechanisms were also investigated by molecular docking.

RESULTS

Twenty-three compounds, including a new phenolic acid uncariarhyine A (1), eight known triterpenoids (2-9), and ten known aromatic derivatives (10, 13-16, and 19-23), were isolated from U. rhynchophylla. Compounds 1-5, 7, 9, and 15 showed significant inhibitory activities against hCE 2 with IC50 values from 4.01  ± 0.61 µM to 18.60 ± 0.21 µM, and their inhibition kinetic analysis results revealed that compounds 1, 5, 9, and 15 were non-competitive; compounds 3 and 4 were mixed-type, and compounds 2 and 7 were uncompetitive. Molecular docking studies indicated inhibition mechanisms of compounds 1-5, 7, 9, and 15 against hCE 2.

CONCLUSION

Our present findings highlight potential natural hCE 2 inhibitors from U. rhynchophylla.

BACKGROUND

Carboxylesterases (CEs) belong to the serine hydrolase family, and are in charge of hydrolyzing chemicals with carboxylic acid ester and amide functional groups via Ser-His-Glu. Uncaria rhynchophylla (Miq.) Miq. ex Havil. is a famous traditional Chinese medicine used in managing hyperpyrexia, epilepsy, preeclampsia, and hypertension in China.

HYPOTHESIS/PURPOSE

To discover the potential natural human carboxylesterase 2 (hCE 2) inhibitors from U. rhynchophylla.

METHODS

Compounds were obtained from the hooks of U. rhynchophylla by silica gel and preparative HPLC. Their structures were elucidated by using HRESIMS, 1D and 2D NMR spectra. Their inhibitory activeties and inhibition kinetics against hCE 2 were assayed by the fluorescent probe, and potential mechanisms were also investigated by molecular docking.

RESULTS

Twenty-three compounds, including a new phenolic acid uncariarhyine A (1), eight known triterpenoids (2-9), and ten known aromatic derivatives (10, 13-16, and 19-23), were isolated from U. rhynchophylla. Compounds 1-5, 7, 9, and 15 showed significant inhibitory activities against hCE 2 with IC50 values from 4.01  ± 0.61 µM to 18.60 ± 0.21 µM, and their inhibition kinetic analysis results revealed that compounds 1, 5, 9, and 15 were non-competitive; compounds 3 and 4 were mixed-type, and compounds 2 and 7 were uncompetitive. Molecular docking studies indicated inhibition mechanisms of compounds 1-5, 7, 9, and 15 against hCE 2.

CONCLUSION

Our present findings highlight potential natural hCE 2 inhibitors from U. rhynchophylla.


获取全文 10.1016/j.phymed.2018.10.006