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Characterization and structure-activity relationship studies of flavonoids as inhibitors against human carboxylesterase 2
Weng, Zi-Miao1; Ge, Guang-Bo2,3; Dou, Tong-Yi3,4; Wang, Ping2; Liu, Ping-Kun1; Tian, Xin-Hui2; Qiao, Nan4; Yu, Yang2; Zou, Li-Wei2; Zhou, Qi1; Zhang, Wei-Dong2; Hou, Jie1
KeywordFlavonoids Human Carboxylesterase 2 (Hce2) Structure-inhibition Relationships Selectivity Inhibition Mechanism
Source PublicationBIOORGANIC CHEMISTRY
2018-04-01
ISSN0045-2068
DOI10.1016/j.bioorg.2018.01.011
Volume77Pages:320-329
Indexed BySCI
SubtypeArticle
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine ; Physical Sciences
WOS SubjectBiochemistry & Molecular Biology ; Chemistry, Organic
WOS Research AreaBiochemistry & Molecular Biology ; Chemistry
WOS KeywordSELECTIVE INHIBITORS ; INTESTINAL CARBOXYLESTERASE ; CATALYTIC-PROPERTIES ; NATURAL INHIBITORS ; INDUCED DIARRHEA ; HUMAN LIVER ; IRINOTECAN ; ISOZYMES ; TRITERPENOIDS ; ACTIVATION
AbstractHuman carboxylesterases (hCEs) are key enzymes from the serine hydrolase superfamily. Among all identified hCEs, human carboxylesterase 2 (hCE2) plays crucial roles in the metabolic activation of ester drugs including irinotecan and flutamide. Selective and potent hCE2 inhibitors could be used to alleviate the toxicity induced by hCE2-substrate drugs. In this study, more than fifty flavonoids were collected to assay their inhibitory effects against hCE2 using a fluorescence-based method. The results demonstrated that C3 and C6 hydroxy groups were essential for hCE2 inhibition, while O-glycosylation or C-glycosylation would lead to the loss of hCE2 inhibition. Among all tested flavonoids, 5,6-dihydroxyflavone displayed the most potent inhibitory effect against hCE2 with the IC50 value of 3.50 mu M. The inhibition mechanism of 5,6-dihydroxyflavone was further investigated by both experimental and docking simulations. All these findings are very helpful for the medicinal chemists to design and develop more potent and highly selective flavonoid-type hCE2 inhibitors. (C) 2018 Published by Elsevier Inc.
Language英语
WOS IDWOS:000428013300034
PublisherACADEMIC PRESS INC ELSEVIER SCIENCE
Citation statistics
Cited Times:13[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://cas-ir.dicp.ac.cn/handle/321008/169109
Collection中国科学院大连化学物理研究所
Corresponding AuthorHou, Jie
Affiliation1.Dalian Med Univ, Dalian 116044, Peoples R China
2.Shanghai Univ Tradit Chinese Med, Inst Interdisciplinary Med, Shanghai 201203, Peoples R China
3.Chinese Acad Sci, Dalian Inst Chem Phys, Dalian 116023, Peoples R China
4.Dalian Univ Technol, Sch Life Sci & Med, Panjin 124221, Peoples R China
Recommended Citation
GB/T 7714
Weng, Zi-Miao,Ge, Guang-Bo,Dou, Tong-Yi,et al. Characterization and structure-activity relationship studies of flavonoids as inhibitors against human carboxylesterase 2[J]. BIOORGANIC CHEMISTRY,2018,77:320-329.
APA Weng, Zi-Miao.,Ge, Guang-Bo.,Dou, Tong-Yi.,Wang, Ping.,Liu, Ping-Kun.,...&Hou, Jie.(2018).Characterization and structure-activity relationship studies of flavonoids as inhibitors against human carboxylesterase 2.BIOORGANIC CHEMISTRY,77,320-329.
MLA Weng, Zi-Miao,et al."Characterization and structure-activity relationship studies of flavonoids as inhibitors against human carboxylesterase 2".BIOORGANIC CHEMISTRY 77(2018):320-329.
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