| Title : Demethylbellidifolin isolated from Swertia bimaculate against human carboxylesterase 2: Kinetics and interaction mechanism merged with docking simulations - Liu_2019_Bioorg.Chem_90_103101 |
| Author(s) : Liu TT , Huo XK , Tian XG , Liang JH , Yi J , Zhang XY , Zhang S , Feng L , Ning J , Zhang BJ , Sun CP , Ma XC |
| Ref : Bioorg Chem , 90 :103101 , 2019 |
|
Abstract :
In this study, forty-nine kinds of traditional Chinese medicines (TCMs) were evaluated for their inhibitory activities against human carboxylesterase 2 (HCE 2) using a human liver microsome (HLM) system. Swertia bimaculata showed significant inhibition on HCE 2 at 10mug/mL among forty-nine kinds of TCMs. The extract of Swertia bimaculata was separated by preparative HPLC to afford demethylbellidifolin (1) identified by MS, (1)H NMR, and (13)C NMR spectra. Demethylbellidifolin (1) was assayed for its inhibitory HCE 2 effect by HCE 2-mediated DDAB hydrolysis, and its potential IC50 value was 3.12+/-0.64muM. Demethylbellidifolin (1) was assigned as a mixed-type competitive inhibitor with the inhibiton constant Ki value of 6.87microM by Lineweaver-Burk and slope plots. Living cell imaging was conducted to corroborate its inhibitory HCE 2 activity. Molecular docking indicated potential interactions of demethylbellidifolin (1) with HCE 2 through two hydrogen bonds of the C-3 and C-5 hydroxy groups with amino acid residues Glu227 and Ser228 in the catalytic cavity, respectively. |
| PubMedSearch : Liu_2019_Bioorg.Chem_90_103101 |
| PubMedID: 31291611 |
| Substrate | DDAB |
Liu TT, Huo XK, Tian XG, Liang JH, Yi J, Zhang XY, Zhang S, Feng L, Ning J, Zhang BJ, Sun CP, Ma XC (2019)
Demethylbellidifolin isolated from Swertia bimaculate against human carboxylesterase 2: Kinetics and interaction mechanism merged with docking simulations
Bioorg Chem
90 :103101
Liu TT, Huo XK, Tian XG, Liang JH, Yi J, Zhang XY, Zhang S, Feng L, Ning J, Zhang BJ, Sun CP, Ma XC (2019)
Bioorg Chem
90 :103101