期刊
JOURNAL OF INORGANIC BIOCHEMISTRY
卷 169, 期 -, 页码 23-31出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jinorgbio.2017.01.001
关键词
Isoquinoline derivatives; Zn(II)/Mn(II) complexes; Crystal structure; Antitumor activity; Action mechanism
资金
- National Natural Science Foundation of China [21271051, 21401031, 21431001, 81473102, IRT1225]
- Natural Science Foundation of Guangxi Province [2014GXNSFBA118035, 2015GXNSFAA139043]
- BAGUI Scholar program of Guangxi, China
- Program for Guangxi Scientific Research of Higher Education [YB20140055]
- Program for Key Scientific Research of Guangxi Normal University [2014ZD005]
- Talent's Small Highland Project of Guangxi Medicinal Industry [1413]
Four 112-CI bridged dinuclear metal complexes with isoquinoline ligands, (MPDQ)(2)Zn2CI4 (1) (MPDQ = 4.5methylenedioxy-1-pyridinedihydroisoquinoline), (PYP)(2)Zn2CI4 (2) (PYP = 5-pyridin-2-y1-11,31dioxolo[4,5asoquinoline), (MPDQ)(2)Mn2CI4 (3),and (PYP)(2)Mn2CI4 (4) were synthesized and characterized. All complexes exhibited strong proliferation inhibition activity against various cancer cells. The underlying molecular mechanisms through which they caused the cancer cell death were also elucidated. Induction of apoptosis in MGC803 cells by complex 2 was evidenced by annexin V/PI detection and DiD/DAPI staining assay. Further investigation revealed that complex 2 was able to induce intrinsic pathway-dependent apoptosis in cancer cells by triggering DNA damage which was caused by the overproduction of reactive oxygen species. Based on these studies, we suggest that Zn(II) complexes containing isoquinoline ligands can be developed as candidates for anti-cancer chemotherapeutics. (C) 2017 Elsevier Inc. All rights reserved.
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