Novel dauricine derivatives suppress cancer via autophagy-dependent cell death

被引:18
作者
Zhou, Xiaobo [1 ,2 ]
Qu, Yuan Qing [1 ,2 ]
Zheng, Zhiyuan [1 ,2 ]
Law, Betty Yuen Kwan [1 ,2 ]
Mok, Simon Wing Fai [1 ,2 ]
Jiang, Zhi-Hong [1 ,2 ]
Wong, Vincent Kam Wai [1 ,2 ]
Bai, Li-Ping [1 ,2 ]
机构
[1] Macau Univ Sci & Technol, State Key Lab Qual Res Chinese Med, Taipa, Macao, Peoples R China
[2] Macau Univ Sci & Technol, Macau Inst Appl Res Med & Hlth, Taipa, Macao, Peoples R China
关键词
Bisbenzylisoquinoline alkaloids; Dauricine derivatives; Carbamate; Autophagy activator; Anti-cancer; AMPK ACTIVATOR; APOPTOSIS; PROLIFERATION; BARRIER; LC3;
D O I
10.1016/j.bioorg.2018.10.074
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
Eleven dauricine derivatives were synthesized and evaluated for their anti-cancer effect in different cancer cells and their autophagic activity in HeLa model cell. Among these newly synthesized compounds, carbamates 2a, 2b, carbonyl ester 3a and sulfonyl ester 4a exhibited potent cytotoxic effects on tested cancer cells with IC50, values ranged from 2.72 to 12.53 mu M, which were more potent than that of dauricine (higher than 15.53 mu M). The above four derivatives are validated to induce autophagy-dependent cell death in HeLa cancer cells. These findings offer us a promising source for generating novel autophagic enhancers for anti-cancer therapy.
引用
收藏
页码:450 / 460
页数:11
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