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铜化合物的潜在生物保护作用:模拟超氧化物歧化酶和过氧化物酶,并抑制酸性磷酸酶作为抗骨质疏松化学疗法的靶点。

Potential bio-protective effect of copper compounds: mimicking SOD and peroxidases enzymes and inhibiting acid phosphatase as a target for anti-osteoporotic chemotherapeutics.

作者信息

Martini Nancy, Parente Juliana E, D Alessandro Franco, Rey Marilin, Rizzi Alberto, Williams Patricia A M, Ferrer Evelina G

机构信息

CEQUINOR, CONICET-CICPBA-UNLP, Faculty of Exact Sciences, National University of La Plata, Bv. 120 No 1465, 1900, La Plata, Argentina.

Physics Department, Faculty of Biochemistry and Biological Sciences, National University of the Litoral, Ciudad Universitaria-Paraje El Pozo, 3000, Santa Fe, Argentina.

出版信息

Mol Biol Rep. 2019 Feb;46(1):867-885. doi: 10.1007/s11033-018-4542-8. Epub 2018 Dec 1.

Abstract

Copper complexes with transformed methimazole ligand have been synthesized and characterized by elemental analysis, conductivity measurements, thermogravimetric analysis, EPR, FTIR and UV-Vis spectroscopies. Results support their stoichiometries and geometrical structures: [Cu(CHNS)Cl]·2HO(1), Cu(CHNS)SOHO and Cu(CHNS)SO. ((CHN)S: bis(l-methylimidazol-2-yl)sulfide; (CHNS) = Bis[bis(l-methylimidazol-2-yl)disulfide]) Concurrently, the structurally distinct soluble species corresponding to complexes (1) and (2) were subsequently used in an in vitro investigation of their potential biological properties. In view of their possible pharmaceutical activity, the complexes were in vitro evaluated as phosphatase acid inhibitors. Their radical bio-protective effects were also studied measuring the effect against DPPH and O radicals. Additional catalytic properties as peroxidase mimics were evaluated using Michaelis-Menten kinetic model by means of phenol red and pyrogallol assays. The complexes exhibited catalytic bromination activity and the ability to oxidize pyrogallol substrate indicating that they can be considered as functional models. The relationships between the structures and the in vitro biological activities have also been considered. Serum protein albumin has attracted the greatest interest as drug carrier and the affinity of biological/pharmaceutical compound is relevant to the development of new medicine. In that sense, interaction studies by fluorescence and EPR spectroscopies were performed showing the binding capacity of the complexes.

摘要

已合成了与转化后的甲巯咪唑配体形成的铜配合物,并通过元素分析、电导率测量、热重分析、电子顺磁共振、傅里叶变换红外光谱和紫外可见光谱对其进行了表征。结果支持了它们的化学计量比和几何结构:[Cu(CHNS)Cl]·2H₂O(1)、Cu(CHNS)₂SO₄·H₂OCu(CHNS)₂SO₄。((CH₂N)₂S:双(1-甲基咪唑-2-基)硫化物;(CHNS)₂ = 双[双(1-甲基咪唑-2-基)二硫化物]) 同时,随后将与配合物(1)和(2)相对应的结构不同的可溶物种用于其潜在生物学性质的体外研究。鉴于它们可能的药物活性,对这些配合物进行了体外磷酸酶酸抑制剂评估。还通过测量对DPPH和O₂自由基的影响研究了它们的自由基生物保护作用。使用米氏动力学模型通过酚红和邻苯三酚测定评估了作为过氧化物酶模拟物的额外催化性质。这些配合物表现出催化溴化活性和氧化邻苯三酚底物的能力,表明它们可被视为功能模型。还考虑了结构与体外生物活性之间的关系。血清蛋白白蛋白作为药物载体引起了最大的关注,生物/药物化合物的亲和力与新药开发相关。从这个意义上说,通过荧光和电子顺磁共振光谱进行了相互作用研究,显示了配合物的结合能力。

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