Syntheses, Crystal Structures, and Antitumor Activities of Copper(II) and Nickel(II) Complexes with 2-((2-(Pyridin-2-yl)hydrazono)methyl)quinolin-8-ol

Qi-Yuan Yang; Qian-Qian Cao; Qi-Pin Qin; Cai-Xing Deng; Hong Liang; Zhen-Feng Chen

doi:10.3390/ijms19071874

Syntheses, Crystal Structures, and Antitumor Activities of Copper(II) and Nickel(II) Complexes with 2-((2-(Pyridin-2-yl)hydrazono)methyl)quinolin-8-ol

Int J Mol Sci. 2018 Jun 26;19(7):1874. doi: 10.3390/ijms19071874.

Authors

Qi-Yuan Yang¹, Qian-Qian Cao², Qi-Pin Qin³, Cai-Xing Deng⁴, Hong Liang⁵, Zhen-Feng Chen⁶

Affiliations

¹ State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmacy, Guangxi Normal University, 15 Yucai Road, Guilin 541004, China. 2016110029@stu.gxnu.edu.cn.
² State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmacy, Guangxi Normal University, 15 Yucai Road, Guilin 541004, China. 2014011049@stu.gxnu.edu.cn.
³ State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmacy, Guangxi Normal University, 15 Yucai Road, Guilin 541004, China. 2014110004@stu.gxnu.edu.cn.
⁴ State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmacy, Guangxi Normal University, 15 Yucai Road, Guilin 541004, China. 2016010981@stu.gxnu.edu.cn.
⁵ State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmacy, Guangxi Normal University, 15 Yucai Road, Guilin 541004, China. hliang@gxnu.edu.cn.
⁶ State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmacy, Guangxi Normal University, 15 Yucai Road, Guilin 541004, China. chenzf@gxnu.edu.cn.

Abstract

Two transition metal complexes with 2-((2-(pyridin-2-yl)hydrazono)methyl)quinolin-8-ol (L), [Cu(L)Cl₂]₂ (1) and [Ni(L)Cl₂]·CH₂Cl₂ (2), were synthesized and fully characterized. Complex 1 exhibited high in vitro antitumor activity against SK-OV-3, MGC80-3 and HeLa cells with IC₅₀ values of 3.69 ± 0.16, 2.60 ± 0.17, and 3.62 ± 0.12 μM, respectively. In addition, complex 1 caused cell arrest in the S phase, which led to the down-regulation of Cdc25 A, Cyclin B, Cyclin A, and CDK2, and the up-regulation of p27, p21, and p53 proteins in MGC80-3 cells. Complex 1 induced MGC80-3 cell apoptosis via a mitochondrial dysfunction pathway, as shown by the significantly decreased level of bcl-2 protein and the loss of Δψ, as well as increased levels of reactive oxygen species (ROS), intracellular Ca²⁺, cytochrome C, apaf-1, caspase-3, and caspase-9 proteins in MGC80-3 cells.

Keywords: apoptosis; copper(II) complex; cytotoxicity; quinolinyl hydrazine.

MeSH terms

Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects
Calcium / metabolism
Caspases / metabolism
Cell Cycle / drug effects
Cell Cycle Proteins / metabolism
Cell Line, Tumor
Coordination Complexes / chemical synthesis*
Coordination Complexes / chemistry
Coordination Complexes / pharmacology*
Copper / chemistry*
Crystallography, X-Ray
Enzyme Activation / drug effects
Humans
Hydrazones / chemical synthesis*
Hydrazones / chemistry
Hydrazones / pharmacology*
Inhibitory Concentration 50
Intracellular Space / metabolism
Membrane Potential, Mitochondrial / drug effects
Nickel / chemistry*
Reactive Oxygen Species / metabolism
Solutions

Substances

Antineoplastic Agents
Cell Cycle Proteins
Coordination Complexes
Hydrazones
Reactive Oxygen Species
Solutions
Copper
Nickel
Caspases
Calcium