KIB OpenIR
Design, synthesis, and biological evaluation of artemyrianolide H derivatives as potential antihepatoma agents
Li,Tian-Ze; Yang,Xiao-Tong; Ma,Wen-Jing; Ma,Yun-Bao; Li,Feng-Jiao; Wang,Yong-Cui; Chen,Ji-Jun
2023
Source PublicationBIOORGANIC CHEMISTRY
ISSN1090-2120
Volume137Pages:106617
AbstractArtemyrianolide H (AH) is a germacrene-type sesquiterpenolid isolated from Artemisia myriantha, and showed potent cytotoxicity against three human hepatocellular carcinoma cell lines HepG2, Huh7, and SK-Hep-1 with IC50 values of 10.9, 7.2, and 11.9 & mu;M, respectively. To reveal structure-activity relationship, 51 artemyrianolide H derivatives including 19 dimeric analogs were designed, synthesized, and assayed for their cytotoxicity against three human hepatoma cell lines. Among them, 34 compounds were more active than artemyrianolide H and sorafenib on the three cell lines. Especially, compound 25 exhibited the most promising activity with IC50 values of 0.7 (HepG2), 0.6 (Huh7), and 1.3 & mu;M (SK-Hep-1), which were 15.5, 12.0, and 9.2-fold higher than that of AH and 16.4, 16.3 and 17.5-fold higher than that of sorafenib. Cytotoxicity evaluation on normal human liver cell lines (THLE-2) demonstrated good safety profile of compound 25 with SI of 1.9 (HepG2), 2.2 (Huh 7) and 1.0 (SK-Hep1). Further studies revealed that compound 25 dose-dependently arrested cells at G2/M phase which was correlated with the up-regulation of both cyclin B1 and p-CDK1, and induced apoptosis through the activation of mitochondrial pathways in HepG2 cells. In addition, the migratory and invasive abilities in HepG2 cells after treatment with 1.5 & mu;M of compound 25 were decreased by 89% and 86% with the increase of E-cadherin expression accompanied by the decrease of N-cadherin, vimentin expression. Bioinformatics analysis based on machine learning predicted that PDGFRA and MAP2K2 might be acting targets of compound 25, and SPR assays demonstrated compound 25 were bound with PDGFRA and MAP2K2 with KD value of 0.168 nM, and 8.49 & mu;M, respectively. This investigation proposed that compound 25 might be considered as a promising lead compound for the development of antihepatoma candidate.
KeywordArtemyrianolide H Germacranolide derivatives Antihepatoma activity Apoptosis DIMERS
Subject AreaBiochemistry & Molecular Biology ; Chemistry
DOI10.1016/j.bioorg.2023.106617
Indexed BySCI
WOS IDWOS:001015397000001
Citation statistics
Document Type期刊论文
Identifierhttp://ir.kib.ac.cn/handle/151853/75475
Collection中国科学院昆明植物研究所
Recommended Citation
GB/T 7714
Li,Tian-Ze,Yang,Xiao-Tong,Ma,Wen-Jing,et al. Design, synthesis, and biological evaluation of artemyrianolide H derivatives as potential antihepatoma agents[J]. BIOORGANIC CHEMISTRY,2023,137:106617.
APA Li,Tian-Ze.,Yang,Xiao-Tong.,Ma,Wen-Jing.,Ma,Yun-Bao.,Li,Feng-Jiao.,...&Chen,Ji-Jun.(2023).Design, synthesis, and biological evaluation of artemyrianolide H derivatives as potential antihepatoma agents.BIOORGANIC CHEMISTRY,137,106617.
MLA Li,Tian-Ze,et al."Design, synthesis, and biological evaluation of artemyrianolide H derivatives as potential antihepatoma agents".BIOORGANIC CHEMISTRY 137(2023):106617.
Files in This Item: Download All
File Name/Size DocType Version Access License
1-s2.0-S004520682300(9670KB)期刊论文出版稿开放获取CC BY-NC-SAView Download
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Li,Tian-Ze]'s Articles
[Yang,Xiao-Tong]'s Articles
[Ma,Wen-Jing]'s Articles
Baidu academic
Similar articles in Baidu academic
[Li,Tian-Ze]'s Articles
[Yang,Xiao-Tong]'s Articles
[Ma,Wen-Jing]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Li,Tian-Ze]'s Articles
[Yang,Xiao-Tong]'s Articles
[Ma,Wen-Jing]'s Articles
Terms of Use
No data!
Social Bookmark/Share
File name: 1-s2.0-S004520682300278X-main.pdf
Format: Adobe PDF
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.