Screening of Cholinesterase Inhibitors in Fructus Evodiae Alkaloids Based on UFLC-MS/molecular Simulation †

doi:10.7503/cjcu20190311

Abstract

Abstract:

Cholinesterase inhibitors targeting acetylcholinesterase and butyryl cholinesterase were screened from alcohol extracts of evodia rutaecarni. The pharmacokinetic process of small molecule compounds in evodia evodia alcohol extract was studied by ultra fast liquid chromatography-mass spectrometry(UFLC-MS). At the same time, UFLC-MS analysis method included specificity, linearity, precision, accuracy, stability, the matrix effect and recovery projects such as a comprehensive inspection. The results show that the method is stable and reliable, and 10 alkaloids compounds in alcohol extract can be absorbed quickly, gastrointestinal tract and the majority of compound blood drug concentration peak at about 1—2 h. Flexible molecular docking and structurally activity analysis of 10 alkaloid compounds with acetylcholinesterase and butylcholinesterase were conducted. It was found that the four compounds with the highest activity were indole-type alkaloids, namely evodiamine, rutaecarpine, dehydroevodiamine and wuchuyuamide Ⅰ, respectively. Their docking scores with acetylcholinesterase were all below -46.02 kJ/mol. The docking scores with butylcholinesterase were all below -41.84 kJ/mol. Evodiamine, rutaecarpine, dehydroevodiamine and wuchuyuamide may be precursor compounds of cholinesterase inhibitors targeting acetylcholinesterase and butyryl cholinesterase.

Key words: Fructus evodiae, Acetylcholinesterase, Butyrylcholinesterase, Ultra fast liquid chromatography-mass spectrometry, Pharmacokinetics in vivo, Molecular docking

CLC Number:

O657

TrendMD:

WANG Lianping,LI Qingjie,LIU Xiaoyan,REN Yueying,YANG Xiuwei. Screening of Cholinesterase Inhibitors in Fructus Evodiae Alkaloids Based on UFLC-MS/molecular Simulation ^†[J]. Chem. J. Chinese Universities, 2020, 41(1): 111.

Figures/Tables 4

References 23

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Compound	Precursor, m/z	Product, m/z	Dwell time/ms	Q₁/V	CE/V	Q₃/V
Dehydroevodiamine	302.05	286.00	40.5	-12.0	-34.0	-30.0
	302.05	287.05	40.5	-12.0	-17.0	-30.0
Evocarpine	340.10	173.10	26.0	-27.0	-21.0	-28.0
	340.10	186.10	26.0	-27.0	-11.0	-23.0
Rutaecarpine	288.05	273.10	26.0	-12.0	-32.0	-29.0
	288.05	115.05	26.0	-12.0	-55.0	-20.0
Wuchuyuamide Ⅰ	352.10	158.10	26.0	-27.0	-21.0	-28.0
	352.10	334.05	26.0	-27.0	-11.0	-23.0
Dihydroevocarpine	342.05	173.10	40.5	-12.0	-23.0	-25.0
	342.05	186.10	40.5	-12.0	-21.0	-16.0
Evodiamine	304.10	134.00	40.5	-12.0	-23.0	-25.0
	304.10	161.00	40.5	-12.0	-21.0	-16.0
1-Methyl-2-nonyl-4(1H)-quinolone	286.05	186.10	40.5	-30.0	-38.0	-19.0
	286.05	131.05	40.5	-30.0	-49.0	-23.0
1-Methyl-2-[Z-6-undecenyl]-4(H)-quinolone	312.20	186.10	26.0	-24.0	-37.0	-19.0
	312.20	173.05	26.0	-24.0	-34.0	-18.0
1-Methyl-2-pentadecadienyl-4(H)-quinolone	366.00	186.10	26.0	-30.0	-41.0	-19.0
	366.00	173.10	26.0	-30.0	-37.0	-17.0
1-Methyl-2-pentadeceny-4(H)-quinolone	368.30	186.10	26.0	-25.0	-37.0	-18.0
	368.30	173.10	26.0	-25.0	-42.0	-19.0

Compound	Precursor, m/z	Product, m/z	Dwell time/ms	Q₁/V	CE/V	Q₃/V
Dehydroevodiamine	302.05	286.00	40.5	-12.0	-34.0	-30.0
	302.05	287.05	40.5	-12.0	-17.0	-30.0
Evocarpine	340.10	173.10	26.0	-27.0	-21.0	-28.0
	340.10	186.10	26.0	-27.0	-11.0	-23.0
Rutaecarpine	288.05	273.10	26.0	-12.0	-32.0	-29.0
	288.05	115.05	26.0	-12.0	-55.0	-20.0
Wuchuyuamide Ⅰ	352.10	158.10	26.0	-27.0	-21.0	-28.0
	352.10	334.05	26.0	-27.0	-11.0	-23.0
Dihydroevocarpine	342.05	173.10	40.5	-12.0	-23.0	-25.0
	342.05	186.10	40.5	-12.0	-21.0	-16.0
Evodiamine	304.10	134.00	40.5	-12.0	-23.0	-25.0
	304.10	161.00	40.5	-12.0	-21.0	-16.0
1-Methyl-2-nonyl-4(1H)-quinolone	286.05	186.10	40.5	-30.0	-38.0	-19.0
	286.05	131.05	40.5	-30.0	-49.0	-23.0
1-Methyl-2-[Z-6-undecenyl]-4(H)-quinolone	312.20	186.10	26.0	-24.0	-37.0	-19.0
	312.20	173.05	26.0	-24.0	-34.0	-18.0
1-Methyl-2-pentadecadienyl-4(H)-quinolone	366.00	186.10	26.0	-30.0	-41.0	-19.0
	366.00	173.10	26.0	-30.0	-37.0	-17.0
1-Methyl-2-pentadeceny-4(H)-quinolone	368.30	186.10	26.0	-25.0	-37.0	-18.0
	368.30	173.10	26.0	-25.0	-42.0	-19.0