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过渡金属单羟基卟啉的 DNA 相互作用和光动力抗肿瘤活性。

DNA interaction and photodynamic antitumor activity of transition metal mono-hydroxyl corrole.

机构信息

School of Chemistry and Chemical Engineering, Key Laboratory of Functional Molecular Engineering of Guangdong Province, South China University of Technology, Guangzhou 510641, China.

Molecular Diagnosis and Treatment Center for Infectious Diseases, Dermatology Hospital, Southern Medical University, Guangzhou 510091, China.

出版信息

Bioorg Chem. 2019 Sep;90:103085. doi: 10.1016/j.bioorg.2019.103085. Epub 2019 Jun 27.

DOI:10.1016/j.bioorg.2019.103085
PMID:31279233
Abstract

A series of iron(III), manganese(III) and copper(III) mono-hydroxyl corrole complexes had been prepared and well characterized by UV-vis, H NMR, F NMR and HR-MS. These metallocorroles may bind to CT-DNA through external binding mode. Metallocorrole Fe-2c exhibited significant phototoxicity and low toxicity toward A549 tumor cells. While manganese (III) and copper (III) corroles showed hypotoxicity to A549, MCF-7 and HepG-2 tumor cells, whether under dark or illumination conditions. All tested metallocorroles exhibited non-toxicity to human normal cells (GES-1) with or without irradiation at 625 nm. Cell cycle analysis indicated that metallocorrole Fe-2c arrested the cell cycle at G2/M phase and increased the Sub-G1 phase in A549 cell lines. It was mainly localized at mitochondria and could significantly reduce mitochondrial membrane potential after photodynamic treatment, which would further induce tumor cell apoptosis.

摘要

一系列铁(III)、锰(III)和铜(III)单羟基卟啉配合物已经被制备并通过紫外可见光谱、氢核磁共振、氟核磁共振和高分辨质谱进行了很好的表征。这些金属卟啉可以通过外部结合模式与 CT-DNA 结合。金属卟啉 Fe-2c 表现出显著的光毒性和低毒性对 A549 肿瘤细胞。而锰(III)和铜(III)卟啉在黑暗或光照条件下对 A549、MCF-7 和 HepG-2 肿瘤细胞均表现出低毒性。所有测试的金属卟啉在 625nm 照射或不照射的情况下对人正常细胞(GES-1)均无毒性。细胞周期分析表明,金属卟啉 Fe-2c 使 A549 细胞周期停滞在 G2/M 期,并增加了 Sub-G1 期。它主要定位于线粒体,在光动力治疗后能显著降低线粒体膜电位,从而进一步诱导肿瘤细胞凋亡。

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