Four copper(II) compounds synthesized by anion regulation: Structure, anticancer function and anticancer mechanism

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

doi:10.1016/j.ejmech.2016.05.021

Four copper(II) compounds synthesized by anion regulation: Structure, anticancer function and anticancer mechanism

Eur J Med Chem. 2016 Oct 4:121:399-409. doi: 10.1016/j.ejmech.2016.05.021. Epub 2016 May 14.

Authors

Zhenlei Zhang¹, Yi Gou², Jun Wang², Kun Yang², Jinxu Qi², Zuping Zhou³, Shichu Liang¹, Hong Liang², Feng Yang⁴

Affiliations

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

PMID: 27309677
DOI: 10.1016/j.ejmech.2016.05.021

Abstract

Copper (Cu) compounds are a promising candidate for next generation metal anticancer drugs. Therefore, we regulated anions to synthesize four mononuclear and binuclear Cu(II) compounds derived from thiosemicarbazone Schiff base ligands and characterized them. 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 and had a capacity to arrest the cell cycle at S phase of those cells. Furthermore, reactive oxygen species (ROS), mitochondrial membrane potential and Western blot analyses revealed that these Cu(II) compounds exert their cytotoxicity through an ROS-mediated intrinsic mitochondrial pathway accompanied by the regulation of Bcl-2 family proteins.

Keywords: Bcl-2 family proteins; Copper compound; Mitochondrial membrane potential; Reactive oxygen species; Thiosemicarbazone Schiff base ligands.

MeSH terms

Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects
Cell Cycle / drug effects
Cell Line, Tumor
Cell Proliferation / drug effects
Chemistry Techniques, Synthetic
Copper / chemistry*
Humans
Membrane Potential, Mitochondrial / drug effects
Models, Molecular
Molecular Conformation
Organometallic Compounds / chemical synthesis*
Organometallic Compounds / chemistry
Organometallic Compounds / pharmacology*
Reactive Oxygen Species / metabolism
Thiosemicarbazones / chemistry

Substances

Antineoplastic Agents
Organometallic Compounds
Reactive Oxygen Species
Thiosemicarbazones
Copper