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基于吡唑啉-吲哚的 Re(I)羰基化合物的生物活性:DNA 相互作用、抗菌、抗癌、ROS 产生、脂质过氧化、体内和体外细胞毒性研究。

Biological activities of pyrazoline-indole based Re(I) carbonyls: DNA interaction, antibacterial, anticancer, ROS production, lipid peroxidation, in vivo and in vitro cytotoxicity studies.

机构信息

Department of Chemistry, Sardar Patel University, Vallabh Vidyanagar, 388120, Gujarat, India.

Department of Biosciences, Sardar Patel University, Vallabh Vidyanagar, Gujarat, India.

出版信息

Chem Biol Interact. 2020 Oct 1;330:109231. doi: 10.1016/j.cbi.2020.109231. Epub 2020 Aug 25.

Abstract

Hetero mononuclear rhenium(I) metal complexes (I-V) using different substituted indole-pyrazoline based ligands were synthesized and characterized by spectroscopic and analytical methods. The binding of the rhenium complexes to Herring sperm DNA was monitored by UV spectroscopy, viscosity measurements, and molecular docking studies; groove binding was suggested as the most possible mode and the DNA-binding constants of the complexes were evaluated. In vivo and in vitro cytotoxicity of compounds were evaluated against the brine shrimp and S. cerevisiae cells. An antimicrobial study was carried out by estimating MIC (Minimum Inhibitory Concentration) against two Gram-positive and three Gram-negative bacteria. All synthesized complexes are biologically more active than the corresponding ligands. The anti-proliferation activity of complexes was evaluated on MCF-7, HCT116, and A549 cancer cells by MTT assay. The toxicity profile of synthesized compounds was confirmed by HO production by reactive oxygen species. The increased concentration of lipid peroxidation end products increased free radicals, which enhancing the oxidative stress level in living organisms and results in cell death.

摘要

使用不同取代的吲哚-吡唑啉基配体合成了异单核铼(I)金属配合物(I-V),并通过光谱和分析方法进行了表征。通过紫外光谱、粘度测量和分子对接研究监测了铼配合物与鲱鱼精子 DNA 的结合;提出了沟结合作为最可能的模式,并评估了配合物的 DNA 结合常数。在体内和体外对化合物进行了对卤虫和 S. cerevisiae 细胞的细胞毒性评估。通过估计对两种革兰氏阳性菌和三种革兰氏阴性菌的最小抑菌浓度 (MIC) 进行了抗菌研究。所有合成的配合物在生物活性上都优于相应的配体。通过 MTT 分析评估了配合物对 MCF-7、HCT116 和 A549 癌细胞的抗增殖活性。通过活性氧产生的 HO 产生证实了合成化合物的毒性概况。脂质过氧化终产物浓度的增加增加了自由基,从而增强了生物体内的氧化应激水平并导致细胞死亡。

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