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

被引：28
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
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