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三(2-吡啶基)吡唑硼酸锌(II)配合物的合成、DNA/蛋白质结合及体外细胞毒性研究。

Tris-(2-pyridyl)-pyrazolyl Borate Zinc(II) Complexes: Synthesis, DNA/Protein Binding and In Vitro Cytotoxicity Studies.

机构信息

Drug Development and Value Creation Research Centre, Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.

Department of Chemistry, National Institute of Technology, Tiruchirappalli 620015, India.

出版信息

Molecules. 2021 Dec 3;26(23):7341. doi: 10.3390/molecules26237341.

Abstract

Zn(II) complexes bearing tris[3-(2-pyridyl)-pyrazolyl] borate (Tp) ligand (-) was synthesized and examined by spectroscopic and analytical tools. Mononuclear [TpZnCl] () has a Zn(II) centre with one arm (pyrazolyl-pyridyl) dangling outside the coordination sphere which is a novel finding in TpZn(II) chemistry. In complex [TpZn(HO)][BF] () hydrogen bonding interaction of aqua moiety stabilizes the dangling arm. In addition, solution state behaviour of complex confirms the tridentate binding mode and reactivity studies show the exogenous axial substituents used to form the [TpZnN] (). The complexes (-) were tested for their ability to bind with Calf thymus (CT) DNA and Bovine serum albumin (BSA) wherein they revealed to exhibit good binding constant values with both the biomolecules in the order of 10-10 M. The intercalative binding mode with CT DNA was confirmed from the UV-Visible absorption, viscosity, and ethidium bromide (EB) DNA displacement studies. Further, the complexes were tested for in vitro cytotoxic ability on four triple-negative breast cancer (TNBC) cell lines (MDA-MB-231, MDA-MB-468, HCC1937, and Hs 578T). All three complexes (-) exhibited good IC values (6.81 to 16.87 μM for 24 h as seen from the MTS assay) results which indicated that these complexes were found to be potential anticancer agents against the TNBC cells.

摘要

含三[3-(2-吡啶基)-吡唑基]硼酸根(Tp)配体(-)的 Zn(II) 配合物通过光谱和分析工具进行了研究。单核[TpZnCl]()具有一个 Zn(II) 中心,一个臂(吡唑基-吡啶基)悬在配位球之外,这是 TpZn(II) 化学中的一个新发现。在配合物[TpZn(HO)][BF]()中,氢键相互作用稳定了悬空臂。此外,配合物的溶液状态行为证实了其三齿配位模式,反应性研究表明,使用外源轴向取代基形成[TpZnN]()。测试了配合物(-)与小牛胸腺(CT)DNA 和牛血清白蛋白(BSA)的结合能力,发现它们与两种生物分子的结合常数值都很好,在 10-10 M 的范围内。通过紫外可见吸收、粘度和溴化乙锭(EB)DNA 置换研究证实了与 CT DNA 的插入结合模式。此外,还测试了这些配合物在四种三阴性乳腺癌(TNBC)细胞系(MDA-MB-231、MDA-MB-468、HCC1937 和 Hs 578T)上的体外细胞毒性能力。所有三种配合物(-)都表现出良好的 IC 值(6.81 至 16.87 μM,在 24 小时的 MTS 测定中可见),这表明这些配合物被发现是针对 TNBC 细胞的潜在抗癌药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4503/8659194/df398cba9bbc/molecules-26-07341-sch001.jpg

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