Synthesis of four binuclear copper(II) complexes: Structure, anticancer properties and anticancer mechanism

Jinxu Qi; Shichu Liang; Yi Gou; Zhenlei Zhang; Zuping Zhou; Feng Yang; Hong Liang

doi:10.1016/j.ejmech.2015.04.031

Synthesis of four binuclear copper(II) complexes: Structure, anticancer properties and anticancer mechanism

Eur J Med Chem. 2015:96:360-8. doi: 10.1016/j.ejmech.2015.04.031. Epub 2015 Apr 14.

Authors

Jinxu Qi¹, Shichu Liang², Yi Gou³, Zhenlei Zhang³, Zuping Zhou², Feng Yang⁴, Hong Liang¹

Affiliations

¹ Key Laboratory of Ecology of Rare an Endangered Species and Environmental Protection, Ministry of Education of the People's Republic of China, Guangxi Normal University, Guilin, Guangxi, China; State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, Ministry of Science and Technology of China, Guanxi Normal University, Guilin, Guangxi, China.
² Key Laboratory of Ecology of Rare an Endangered Species and Environmental Protection, Ministry of Education of the People's Republic of China, Guangxi Normal University, Guilin, Guangxi, China.
³ State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, Ministry of Science and Technology of China, Guanxi Normal University, Guilin, Guangxi, China.
⁴ Key Laboratory of Ecology of Rare an Endangered Species and Environmental Protection, Ministry of Education of the People's Republic of China, Guangxi Normal University, Guilin, Guangxi, China; State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, Ministry of Science and Technology of China, Guanxi Normal University, Guilin, Guangxi, China. Electronic address: fyang@mailbox.gxnu.edu.cn.

PMID: 25899339
DOI: 10.1016/j.ejmech.2015.04.031

Abstract

Copper (Cu) compounds are a promising candidate for next generation metal anticancer drugs and have been extensively studied. Therefore, four binuclear copper(II) compounds derived from Schiff base thiosemicarbazones (L1-L4), namely [CuCl(L1)]2 (C1), [CuNO3(L2)]2 (C2), [Cu(NCS) (L3)]2 (C3) and [Cu(CH3COO) (L4)]2 (C4) were synthesized and characterized. Four of these compounds showed very high cytotoxicity to cancer cell lines in vitro. These Cu(II) compounds strongly promoted the apoptosis of BEL-7404 cells. The formation of reactive oxygen species (ROS), change in mitochondrial membrane potential and western blot analysis revealed that Cu compounds could induce cancer cell apoptosis through the intrinsic ROS-mediated mitochondrial pathway accompanied by the regulation of Bcl-2 family proteins.

Keywords: Anticancer activity; Anticancer mechanism; Bcl-2 family proteins; Cell apoptosis; Copper(II) complex.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects
Cell Line, Tumor
Cell Proliferation / drug effects
Copper / chemistry*
Crystallography, X-Ray
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Humans
Models, Molecular
Molecular Structure
Organometallic Compounds / chemical synthesis
Organometallic Compounds / chemistry
Organometallic Compounds / pharmacology*
Reactive Oxygen Species / metabolism
Structure-Activity Relationship

Substances

Antineoplastic Agents
Organometallic Compounds
Reactive Oxygen Species
Copper