Synthesis of Ergosterol Peroxide Conjugates as Mitochondria Targeting Probes for Enhanced Anticancer Activity

被引：29
作者：
Bu, Ming [1 ]
Li, Hongling [1 ]
Wang, Haijun [1 ]
Wang, Jing [1 ]
Lin, Yu [1 ]
Ma, Yukun [2 ]
机构：
[1] Qiqihar Med Univ, Coll Pharm, Qiqihar 161006, Peoples R China
[2] Qiqihar Med Univ, Res Inst Med & Pharm, Qiqihar 161006, Peoples R China
来源：
MOLECULES | 2019年 / 24卷 / 18期
关键词：
ergosterol peroxide; target probe; mitochondria; fluorescence imaging; antitumor activity; BIOLOGICAL EVALUATION; SIDE-CHAIN; DERIVATIVES; ACTIVATION; APOPTOSIS; STRESS;
D O I：
10.3390/molecules24183307
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Inspired by the significant bioactivity of ergosterol peroxide, we designed and synthesized four fluorescent coumarin and ergosterol peroxide conjugates 8a-d through the combination of ergosterol peroxide with 7-N,N-diethylamino coumarins fluorophore. The cytotoxicity of synthesized conjugates against three human cancer cells (HepG2, SK-Hep1, and MCF-7) was evaluated. The results of fluorescent imaging showed that the synthesized conjugates 8a-d localized and enriched mainly in mitochondria, leading to significantly enhanced cytotoxicity over ergosterol peroxide. Furthermore, the results of biological functions of 8d showed that it could suppress cell colony formation, invasion, and migration; induce G2/M phase arrest of HepG2 cells, and increase the intracellular ROS level.
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页数：15
相关论文
共 41 条
[1]  
[Anonymous], 2014, ANGEW CHEM, DOI DOI 10.1002/ANGE.201408897
[2]   Intermediates in the cleavage of endoperoxides [J].
Bauch, Marcel ;
Klaper, Matthias ;
Linker, Torsten .
JOURNAL OF PHYSICAL ORGANIC CHEMISTRY, 2017, 30 (04)
[3]   Synthesis and biological evaluation of novel steroidal 5α,8α-epidioxyandrost-6-ene-3β-ol-17-(O-phenylacetamide)oxime derivatives as potential anticancer agents [J].
Bu, Ming ;
Cao, Tingting ;
Li, Hongxia ;
Guo, Mingzhou ;
Yang, Burton B. ;
Zeng, Chengchu ;
Zhou, Yue ;
Zhang, Na ;
Hu, Liming .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2017, 27 (16) :3856-3861
[4]   Synthesis and biological evaluation of novel steroidal 5α,8α-endoperoxide derivatives with aliphatic side-chain as potential anticancer agents [J].
Bu, Ming ;
Cao, Tingting ;
Li, Hongxia ;
Guo, Mingzhou ;
Yang, Burton B. ;
Zhou, Yue ;
Zhang, Na ;
Zeng, Chengchu ;
Hu, Liming .
STEROIDS, 2017, 124 :46-53
[5]   Synthesis of 5α,8α-Ergosterol Peroxide 3-Carbamate Derivatives and a Fluorescent Mitochondria-Targeting Conjugate for Enhanced Anticancer Activities [J].
Bu, Ming ;
Cao, Tingting ;
Li, Hongxia ;
Guo, Mingzhou ;
Yang, Burton B. ;
Zeng, Chengchu ;
Hu, Liming .
CHEMMEDCHEM, 2017, 12 (06) :466-474
[6]   Natural Endoperoxides as Drug Lead Compounds [J].
Bu, Ming ;
Yang, Burton B. ;
Hu, Liming .
CURRENT MEDICINAL CHEMISTRY, 2016, 23 (04) :383-405
[7]  
Callaway E, 2015, NATURE, V526, P174, DOI 10.1038/nature.2015.18507
[8]   Photocatalytic Hydrogen Production using Polymeric Carbon Nitride with a Hydrogenase and a Bioinspired Synthetic Ni Catalyst [J].
Caputo, Christine A. ;
Gross, Manuela A. ;
Lau, Vincent W. ;
Cavazza, Christine ;
Lotsch, Bettina V. ;
Reisner, Erwin .
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2014, 53 (43) :11538-11542
[9]   Synthesis, characterization and antitumor activities of some steroidal derivatives with side chain of 17-hydrazone aromatic heterocycle [J].
Cui, Jianguo ;
Liu, Liang ;
Zhao, Dandan ;
Gan, Chunfang ;
Huang, Xin ;
Xiao, Qi ;
Qi, Binbin ;
Yang, Lei ;
Huang, Yanmin .
STEROIDS, 2015, 95 :32-38
[10]   Two new withanolides from the halophyte Datura stramonium L. [J].
Fang, Sheng-Tao ;
Liu, Xia ;
Kong, Na-Na ;
Liu, Su-Jing ;
Xia, Chuan-Hai .
NATURAL PRODUCT RESEARCH, 2013, 27 (21) :1965-1970
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