Wang Feng-Yang, Xi Qian-Yu, Huang Ke-Bin, Tang Xiao-Ming, Chen Zhen-Feng, Liu Yan-Cheng, Liang Hong
Guangxi Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry & Chemical Engineering of Guangxi Normal University, Guilin 541004, PR China.
Guangxi Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry & Chemical Engineering of Guangxi Normal University, Guilin 541004, PR China.
J Inorg Biochem. 2017 Apr;169:23-31. doi: 10.1016/j.jinorgbio.2017.01.001. Epub 2017 Jan 6.
Four μ-Cl bridged dinuclear metal complexes with isoquinoline ligands, (MPDQ)ZnCl (1) (MPDQ=4.5-methylenedioxy-1-pyridinedihydroisoquinoline), (PYP)ZnCl (2) (PYP=5-pyridin-2-yl-[1,3]dioxolo[4,5-g]isoquinoline), (MPDQ)MnCl (3),and (PYP)MnCl (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 MGC-803 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.
合成并表征了四种含异喹啉配体的μ-Cl桥连双核金属配合物，即(MPDQ)ZnCl (1)（MPDQ = 4,5-亚甲基二氧基-1-吡啶二氢异喹啉）、(PYP)ZnCl (2)（PYP = 5-吡啶-2-基-[1,3]二氧杂环戊烯并[4,5-g]异喹啉）、(MPDQ)MnCl (3)和(PYP)MnCl (4)。所有配合物对多种癌细胞均表现出较强的增殖抑制活性。还阐明了它们导致癌细胞死亡的潜在分子机制。通过膜联蛋白V/PI检测和DiD/DAPI染色试验证明了配合物2诱导MGC-803细胞凋亡。进一步研究表明，配合物2能够通过引发由活性氧过度产生导致的DNA损伤，在癌细胞中诱导内源性途径依赖性凋亡。基于这些研究，我们认为含异喹啉配体的Zn(II)配合物可开发成为抗癌化学治疗药物的候选物。
