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通过肾素-血管紧张素系统 (RAS) 调节的氨肽酶研究吡啶-2-甲醛和 5,6-二氨基-1,3-二甲基尿嘧啶衍生的席夫碱的 Ni(II)、Zn(II) 和 Cd(II) 配合物对雌激素依赖性和三阴性乳腺癌细胞生长的影响。

Effects on estrogen-dependent and triple negative breast cancer cells growth of Ni(II), Zn(II) and Cd(II) complexes with the Schiff base derived from pyridine-2-carboxaldehyde and 5,6-diamino-1,3-dimethyluracil explored through the renin-angiotensin system (RAS)-regulating aminopeptidases.

机构信息

Department of Inorganic and Organic Chemistry, University of Jaén, Jaén, Spain.

Department of Health Sciences, University of Jaén, Jaén, Spain.

出版信息

J Inorg Biochem. 2018 Aug;185:52-62. doi: 10.1016/j.jinorgbio.2018.04.022. Epub 2018 May 9.

Abstract

A series of Ni(II), Zn(II) and Cd(II) complexes with the Schiff base derived from the condensation 1:1 from pyridine-2-carboxaldehyde and 5,6-diamino-1,3-dimethyluracil (6-amino-1,3-dimethyl-5-[(pyridin-2-ylmethylidene)-amino]pyrimidine-2,4(1H,3H)-dione, DAAUPic) were synthesized and subsequently characterized by means of elemental analysis, FT-IR, NMR and nine of them by X-ray diffraction. Except the [Zn(μ-O,O'-AcO)(N,N,N-DAAUPicH)] and [Cd(O,O'-NO)(μ-O,(N,N,N)-DAAUPicH)(HO)]·2HO dimers and the [Cd(μ-S,N-SCN)(N,N,N-DAAUPicH)] chain-like polymer, all of them display monomeric molecular structures. The anticancer activity of compounds was also explored studying their effects on renin-angiotensin system (RAS)-regulating aminopeptidases on estrogen-dependent and triple negative breast cancer cell lines. At the concentrations used, some of the complexes showed different effects on (RAS) peptidases, which support the idea that their effects on cell growth/proliferation could be related to autocrine/paracrine regulatory functions of their corresponding peptide substrates.

摘要

一系列的 Ni(II)、Zn(II) 和 Cd(II) 配合物是由吡啶-2-甲醛和 5,6-二氨基-1,3-二甲基尿嘧啶(6-氨基-1,3-二甲基-5-[(吡啶-2-亚甲基)-氨基]嘧啶-2,4(1H,3H)-二酮,DAAUPic)缩合而成的,并用元素分析、FT-IR、NMR 进行了表征,其中有 9 个配合物还通过 X 射线衍射进行了表征。除了[Zn(μ-O,O'-AcO)(N,N,N-DAAUPicH)]和[Cd(O,O'-NO)(μ-O,(N,N,N)-DAAUPicH)(HO)]·2HO 二聚体和[Cd(μ-S,N-SCN)(N,N,N-DAAUPicH)]链状聚合物之外,所有这些配合物都呈现出单体的分子结构。还研究了化合物对肾素-血管紧张素系统(RAS)调节的氨肽酶在雌激素依赖性和三阴性乳腺癌细胞系中的作用,以探索它们的抗癌活性。在使用的浓度下,一些配合物对(RAS)肽酶表现出不同的影响,这支持了它们对细胞生长/增殖的影响可能与其相应肽底物的自分泌/旁分泌调节功能有关的观点。

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