Synthesis, characterization and antitumor mechanism investigation of ruthenium(II) polypyridyl complexes with artesunate moiety

被引：11

作者：

Chen, Bi-Chun ^{[1
]}

Lu, Jun-Jian ^{[1
]}

Jiang, Ning ^{[1
]}

Ma, Xiu-Rong ^{[1
]}

Li, Rong-Tao ^{[1
]}

Ye, Rui-Rong ^{[1
]}

机构：

[1] Kunming Univ Sci & Technol, Fac Life Sci & Technol, Kunming 650500, Yunnan, Peoples R China

来源：

JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY | 2021年 / 26卷 / 08期

基金：

中国国家自然科学基金;

关键词：

Ruthenium(II) complexes; Artesunate; Anticancer activity; Apoptosis; Autophagy; CELLULAR UPTAKE; ANTICANCER ACTIVITY; AUTOPHAGY; CANCER; APOPTOSIS; DRUG; DEATH; ROS; LIPOPHILICITY; MITOCHONDRIA;

D O I：

10.1007/s00775-021-01901-8

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：

Six artesunate (ART) conjugated ruthenium(II) complexes (Ru(II)-ART conjugates) with the formula [Ru(N<^>N)(2)bpy(4-CH3-4'-CH(2)OART)](PF6)(2) (Ru-ART-1-3) and [Ru(N<^>N)(2)bpy(4-CH(2)OART-4'-CH(2)OART)](PF6)(2) (Ru-ART-4-6) (N<^>N = 2,2'-bipyridine (bpy, in Ru-ART-1 and Ru-ART-4), 1,10-phenanthroline (phen, in Ru-ART-2 and Ru-ART-5) and 4,7-diphenyl-1,10-phenanthroline (DIP, in Ru-ART-3 and Ru-ART-6)), were synthesized and characterized. Among them, Ru-ART-1-3 and Ru-ART-4-6 carry one and two ART moieties, respectively. Ru-ART-3 and Ru-ART-6 exhibit better cytotoxicity among six Ru(II)-ART conjugates. These two complexes can be effectively taken up by human cervical carcinoma (HeLa) cells. In addition, they selectively kill cancer cell lines while mildly affect normal cells. Mechanism studies have shown that HeLa cells treated with Ru-ART-3 and Ru-ART-6 show typical apoptotic characteristics (morphology changes, mitochondrial dysfunction, caspase cascade, etc.). On the other hand, the up regulation of Beclin-1 and conversion of LC3-I to LC3-II note the appearance of autophagy. As a result, Ru-ART-3 and Ru-ART-6 induce autophagy-dependent cell apoptosis via mitochondrial dysfunction and reactive oxygen species (ROS) accumulation.

引用

页码：909 / 918

页数：10

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