Construction and application of pharmacophore model of human carboxylesterase 2 inhibitors.
10.19540/j.cnki.cjcmm.20190603.203
- Author:
Jing-Fang ZHANG
1
;
Yan-Cheng LI
1
;
Gui-Yang XIA
1
;
Yun-Qing SONG
2
;
Ling-Yan WANG
1
;
Peng-Cheng LIN
3
;
Guang-Bo GE
2
;
Sheng LIN
1
Author Information
1. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100050, China.
2. Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine Shanghai 201203, China.
3. College of Pharmaceutical Sciences, Qinghai University for Nationalities Xining 810007, China.
- Publication Type:Journal Article
- Keywords:
Paeonia lactiflora;
hCE2 inhibitors;
human carboxylesterase 2;
pharmacophore model
- MeSH:
Carboxylesterase/metabolism*;
Humans;
Hydrogen Bonding;
Hydrophobic and Hydrophilic Interactions
- From:
China Journal of Chinese Materia Medica
2021;46(3):638-644
- CountryChina
- Language:Chinese
-
Abstract:
According to human carboxylesterase 2(hCE2) inhibitors reported in the literature, the pharmacophore model of hCE2 inhibitors was developed using HipHop module in Discovery Studio 2016. The optimized pharmacophore model, which was validated by test set, contained two hydrophobic, one hydrogen bond acceptor, and one aromatic ring features. Using the pharmacophore model established, 5 potential hCE2 inhibitors(CS-1,CS-2,CS-3,CS-6 and CS-8) were screened from 20 compounds isolated from the roots of Paeonia lactiflora, which were further confirmed in vitro, with the IC_(50) values of 5.04, 5.21, 5.95, 6.64 and 7.94 μmol·L~(-1), respectively. The results demonstrated that the pharmacophore model exerted excellent forecasting ability with high precision, which could be applied to screen novel hCE2 inhibitors from Chinese medicinal materials.
