Demethylbellidifolin isolated from Swertia bimaculate against human carboxylesterase 2: Kinetics and interaction mechanism merged with docking simulations |
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| Affiliation: | 1. College of Pharmacy, College (Institute) of Integrative Medicine, The National & Local Joint Engineering Research Center for Drug Development of Neurodegenerative Disease, Dalian Medical University, Dalian, China;2. Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China;1. Institute of Physiologically Active Compounds Russian Academy of Sciences, Chernogolovka 142432, Russia;2. Emanuel Institute of Biochemical Physics Russian Academy of Sciences, Moscow 119334, Russia;3. Institute of Problems of Chemical Physics Russian Academy of Sciences, Chernogolovka 142432, Russia;4. Department of Environmental Health Sciences, University of Michigan, Ann Arbor, MI 48109, USA;5. Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA;1. School of Chemical Engineering and Material Science, Tianjin University of Science and Technology, 13St. 29, TEDA, 300457, Tianjin, PR China;2. School of Marine and Environmental Science, Tianjin Marine Environmental Protection and Restoration Technology Engineering Center, Tianjin University of Science and Technology, 13St. 29, TEDA, 300457, Tianjin, PR China;1. College of Pharmacy, College (Institute) of Integrative Medicine, Advanced Institute for Medical Sciences, Dalian Medical University, Dalian, 116044, People''s Republic of China;2. Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221004, People''s Republic of China;3. Key Laboratory of Biotechnology and Bioresources Utilization, Ministry of Education, College of Life Science, Dalian Minzu University, Dalian, 116600, People''s Republic of China;1. Dalian Key Laboratory of Metabolic Target Characterization and Traditional Chinese Medicine Intervention, College of Pharmacy, College of Integrative Medicine, Dalian Medical University, Dalian 116044, China;2. Second Affiliated Hospital, Dalian Medical University, Dalian 116044, China;3. School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China;1. Dalian Medical University, Dalian 116044, China;2. Institute of Interdisciplinary Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China;3. Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China;4. School of Life Science and Medicine, Dalian University of Technology, Panjin 124221, China |
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| 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 10 μg/mL among forty-nine kinds of TCMs. The extract of Swertia bimaculata was separated by preparative HPLC to afford demethylbellidifolin (1) identified by MS, 1H NMR, and 13C 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 ± 0.64 μM. Demethylbellidifolin (1) was assigned as a mixed-type competitive inhibitor with the inhibiton constant Ki value of 6.87 µM 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. |
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| Keywords: | HCE 2 Inhibitor Molecular docking Traditional Chinese medicines |
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