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二硫代卡巴腙-铁、-钴、-镍和-锌配合物:设计、合成、结构及抗癌评估

Dithiocarbazate-Fe, -Co, -Ni, and -Zn Complexes: Design, Synthesis, Structure, and Anticancer Evaluation.

作者信息

Gou Yi, Jia Xiaoying, Hou Li Xia, Deng Jun Gang, Huang Guo Jin, Jiang Hao Wen, Yang Feng

机构信息

Laboratory of Respiratory Disease, Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi, China.

State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Sciences, Guangxi Norma University, Guilin 541004, Guangxi, China.

出版信息

J Med Chem. 2022 May 12;65(9):6677-6689. doi: 10.1021/acs.jmedchem.1c02186. Epub 2022 Apr 21.

Abstract

Non-platinum-metal complexes show great potential as anticancer agents. Herein, a series of dithiocarbazate non-Pt-metal complexes, including [Fe(L)]·Cl·2HO , [Co(L)]·NO·2.5HO , [Ni(L)] , and [Zn(L)] , have been designed and evaluated for their efficacy as antineoplastic agents. Among them, complex exhibited higher anticancer efficacy than complexes , , , and platin against several cancer cell lines. Hemolysis assays revealed that complex showed comparable hemolysis with platin. anticancer evaluations showed that complex could retard tumor xenograft growth effectively with low systemic toxicity. Further studies revealed that complex suppressed cancer cells by triggering multiple mechanisms involving the simultaneous inhibition of mitochondria and glycolytic bioenergetics. Overall, our study provides new insights into the anticancer mechanism of Co complexes, which can be used as a good strategy to overcome the flexibility of cancer cells to chemotherapy adaptation.

摘要

非铂金属配合物作为抗癌剂显示出巨大潜力。在此,设计并评估了一系列二硫代氨基甲酸盐非铂金属配合物,包括[Fe(L)]·Cl·2H₂O、[Co(L)]·NO₃·2.5H₂O、[Ni(L)]和[Zn(L)]作为抗肿瘤剂的功效。其中,配合物 对几种癌细胞系表现出比配合物 、 、 和铂更高的抗癌功效。溶血试验表明,配合物 与铂表现出相当的溶血作用。抗癌评估表明,配合物 可以有效延缓肿瘤异种移植生长,且全身毒性较低。进一步研究表明,配合物 通过触发多种机制抑制癌细胞,这些机制包括同时抑制线粒体和糖酵解生物能量学。总体而言,我们的研究为钴配合物的抗癌机制提供了新见解,这可作为克服癌细胞对化疗适应性灵活性的良好策略。

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