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银(I)二肽配合物的抗菌和抗癌应用。

Antimicrobial and Anticancer Application of Silver(I) Dipeptide Complexes.

机构信息

Department of Inorganic Chemistry, P. J. Šafárik University, Moyzesova 11, 041 54 Kosice, Slovakia.

Department of Inorganic Chemistry, Charles University, Hlavova 2030, 128 00 Praque, Czech Republic.

出版信息

Molecules. 2021 Oct 20;26(21):6335. doi: 10.3390/molecules26216335.

Abstract

Three silver(I) dipeptide complexes Ag(GlyGly) (AgGlyGly), [Ag(GlyAla)(NO)] (AgGlyAla) and [Ag(HGlyAsp)(NO)] (AgGlyAsp) were prepared, investigated and characterized by vibrational spectroscopy (mid-IR), elemental and thermogravimetric analysis and mass spectrometry. For AgGlyGly, X-ray crystallography was also performed. Their stability in biological testing media was verified by time-dependent NMR measurements. Their in vitro antimicrobial activity was evaluated against selected pathogenic microorganisms. Moreover, the influence of silver(I) dipeptide complexes on microbial film formation was described. Further, the cytotoxicity of the complexes against selected cancer cells (BLM, MDA-MB-231, HeLa, HCT116, MCF-7 and Jurkat) and fibroblasts (BJ-5ta) using a colorimetric MTS assay was tested, and the selectivity index (SI) was identified. The mechanism of action of Ag(I) dipeptide complexes was elucidated and discussed by the study in terms of their binding affinity toward the CT DNA, the ability to cleave the DNA and the ability to influence numbers of cells within each cell cycle phase. The new silver(I) dipeptide complexes are able to bind into DNA by noncovalent interaction, and the topoisomerase I inhibition study showed that the studied complexes inhibit its activity at a concentration of 15 μM.

摘要

三种银(I)二肽配合物Ag(GlyGly)(AgGlyGly)、[Ag(GlyAla)(NO)](AgGlyAla)和[Ag(HGlyAsp)(NO)](AgGlyAsp)被制备、研究和通过振动光谱(中红外)、元素和热重分析及质谱进行了表征。对于 AgGlyGly,还进行了 X 射线晶体学。通过时间依赖性 NMR 测量验证了它们在生物测试介质中的稳定性。评估了它们对选定致病微生物的体外抗菌活性。此外,还描述了银(I)二肽配合物对微生物膜形成的影响。进一步,使用比色 MTS 测定法测试了这些配合物对选定癌细胞(BLM、MDA-MB-231、HeLa、HCT116、MCF-7 和 Jurkat)和成纤维细胞(BJ-5ta)的细胞毒性,并确定了选择性指数(SI)。通过研究它们与 CT DNA 的结合亲和力、切割 DNA 的能力以及影响每个细胞周期相的细胞数量的能力,从作用机制方面阐明和讨论了银(I)二肽配合物的作用机制。新的银(I)二肽配合物能够通过非共价相互作用结合到 DNA 中,拓扑异构酶 I 抑制研究表明,所研究的配合物在 15 μM 的浓度下抑制其活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f35c/8587849/67f638c2231b/molecules-26-06335-g001.jpg

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