α-N-heterocyclic thiosemicarbazone Fe(III) complex: Characterization of its antitumor activity and identification of anticancer mechanism

被引：76

作者：

Gou, Yi ^{[1
]}

Wang, Jun ^{[1
]}

Chen, Shifang ^{[1
]}

Zhang, Zhan ^{[1
]}

Zhang, Yao ^{[1
]}

Zhang, Wei ^{[1
]}

Yang, Feng ^{[1
]}

机构：

[1] Nantong Univ, Sch Pharm, Nantong, Jiangsu, Peoples R China

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2016年 / 123卷

关键词：

Iron(III) complex; alpha-N-heterocyclic thiosemicarbazone; DNA cleavage; Anticancer activity; Anticancer mechanism; IRON OVERLOAD DISEASE; RIBONUCLEOTIDE REDUCTASE; REDOX ACTIVITY; PHASE-II; CHELATORS; CANCER; CELL; SERIES; DENSITY; POTENT;

D O I：

10.1016/j.ejmech.2016.07.041

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We synthesized an alpha-N-heterocyclic thiosemicarbazone ligand (L) and its Fe complex (C1) and assessed their chemical and biological properties in order to understand their marked activity. Electrochemical studies and ascorbate oxidation studies demonstrated that C1 shows considerable redox activity, and Fe-III/II redox potentials was within the range accessible to cellular oxidants and reductants. Absorption spectral, emission spectral and viscosity analysis reveal that L and C1 interacted with DNA through intercalation and C1 exhibited a higher DNA binding ability: Agarose gel electrophoresis experiments indicated that C1 exhibited the highest pBR322 DNA cleaving ability. In vitro, C1 showed significantly more anticancer activity than the ligand alone. Moreover, C1 induces production of reactive oxygen species (ROS) and DNA damage, resulting in activation of the p53 pathway, cell cycle arrest at the S phase, and mitochondria-mediated apoptosis by regulating the expression of Bcl-2 family proteins. (C) 2016 Elsevier Masson SAS. All rights reserved.

引用

页码：354 / 364

页数：11

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