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Structure-activity relationships of cryptopleurine analogs with E-ring modifications as anti-hepatitis C virus agents
Wang, Ying1,2; Chen, Shao-Ru2; Yang, Xiaoming3; Lee, Kuo-Hsiung3,4; Cheng, Yung-Chi1
2018-02
Source PublicationBIOORGANIC & MEDICINAL CHEMISTRY
ISSN0968-0896
Volume26Issue:3Pages:630-636
Abstract

The tylophorine analog rac-cryptopleurine exhibited potent anti-hepatitis C virus (HCV) activity through allosteric regulation of ATPase activity of heat shock cognate protein 70 (Hsc70). We evaluated the impact of modifications on the E-ring of rac-cryptopleurine to the inhibitory activity against HCV replication and regulation of ATPase activity of Hsc70. Cryptopleurine analog YXM-110 with a 13 alpha-hydroxyl group maintained activity against HCV and promoted ATP/ADP turnover of Hsc70; however, compounds with hydroxyl groups at other positions or with other orientations (YXM-109, YXM-139, and YXM-140) did not exhibit similar activities. Size modification or heteroatom incorporation of the E-ring led to loss of anti-HCV activity. Promotion of the chaperone activity of Hsc70 with carboxyl terminus Hsc70 interacting protein (CHIP) further enhanced the anti-HCV activity of rac-cryptopleurine and XYM-110. This structure-activity relationship (SAR) study refined structural design and optimization for developing rac-crytopleurine analogs as potent anti-HCV agents targeted against the host factor involved in HCV replication. (C) 2017 Elsevier Ltd. All rights reserved.

DOI10.1016/j.bmc.2017.12.027
URLView the original
Indexed BySCI
Language英语
WOS Research AreaBiochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Chemistry
WOS SubjectBiochemistry & Molecular Biology ; Chemistry, Medicinal ; Chemistry, Organic
WOS IDWOS:000425550800010
PublisherPERGAMON-ELSEVIER SCIENCE LTD
The Source to ArticleWOS
Fulltext Access
Citation statistics
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorLee, Kuo-Hsiung; Cheng, Yung-Chi
Affiliation1.Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520, United States
2.Institute of Chinese Medical Sciences and State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Macau
3.Natural Products Research Laboratories, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, United States
4.Chinese Medicine Research and Development Center, China Medical University and Hospital, Taichung, Taiwan
First Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Wang, Ying,Chen, Shao-Ru,Yang, Xiaoming,et al. Structure-activity relationships of cryptopleurine analogs with E-ring modifications as anti-hepatitis C virus agents[J]. BIOORGANIC & MEDICINAL CHEMISTRY,2018,26(3):630-636.
APA Wang, Ying,Chen, Shao-Ru,Yang, Xiaoming,Lee, Kuo-Hsiung,&Cheng, Yung-Chi.(2018).Structure-activity relationships of cryptopleurine analogs with E-ring modifications as anti-hepatitis C virus agents.BIOORGANIC & MEDICINAL CHEMISTRY,26(3),630-636.
MLA Wang, Ying,et al."Structure-activity relationships of cryptopleurine analogs with E-ring modifications as anti-hepatitis C virus agents".BIOORGANIC & MEDICINAL CHEMISTRY 26.3(2018):630-636.
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