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合成、结构表征及部分取代胍同核铜(II)配合物的体外生物筛选。

Synthesis, structural characterization and in vitro biological screening of some homoleptic copper(II) complexes with substituted guanidines.

机构信息

Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan.

出版信息

Eur J Med Chem. 2012 Feb;48:26-35. doi: 10.1016/j.ejmech.2011.11.029. Epub 2011 Dec 1.

Abstract

A series of homoleptic copper(II) complexes (1a-8a) with N,N',N″-trisubstituted guanidines, [Cu(II){PhCONHC(NHR)NPh}(2)] (where R = phenyl (1a), n-butyl (2a), sec-butyl (3a), cyclohexyl (4a), 1-naphthyl (5a), 2,4-dichlorophenyl (6a), 3,4-dichlorophenyl (7a), and 3,5-dichlorophenyl (8a)) have been synthesized and characterized by elemental analyses, FT-IR, UV-visible, (1)H and (13)C NMR spectroscopy, and single crystal X-ray diffraction analysis. The X-ray crystal structures revealed that the complexes 2a and 4a are mononuclear in the solid state and that the geometry around the copper atom is nearly square planar. In both the cases, N,N',N″-trisubstituted guanidine ligands have been coordinated to the Cu(II) through the oxygen and nitrogen atoms. The synthesized guanidines and their complexes were initially screened for their anti-microbial activities, and Brine Shrimps Lethality assay. The complexes were also screened for in vitro cytotoxicity activity in human cell lines carcinomas A498, EVSAT, H226, IGROV, M19, MCF-7 and WIDR. The results show a moderate level of cytotoxicity against these seven human cancer cell lines as compared with standard chemotherapeutic drugs.

摘要

一系列具有 N,N',N″-三取代胍的均配铜(II)配合物(1a-8a),[Cu(II){PhCONHC(NHR)NPh}(2)](其中 R = 苯基(1a)、正丁基(2a)、仲丁基(3a)、环己基(4a)、1-萘基(5a)、2,4-二氯苯基(6a)、3,4-二氯苯基(7a)和 3,5-二氯苯基(8a))已通过元素分析、FT-IR、UV-可见、(1)H 和(13)C NMR 光谱和单晶 X 射线衍射分析进行了合成和表征。X 射线晶体结构表明,配合物 2a 和 4a 在固态中为单核,铜原子周围的几何形状几乎为正方形平面。在这两种情况下,N,N',N″-三取代胍配体均通过氧和氮原子与 Cu(II)配位。最初对合成的胍及其配合物进行了抗微生物活性和盐水虾致死性测定筛选。还对这些配合物在人类癌细胞系 A498、EVSAT、H226、IGROV、M19、MCF-7 和 WIDR 中的体外细胞毒性活性进行了筛选。与标准化疗药物相比,这些配合物对这七种人类癌细胞系表现出中等水平的细胞毒性。

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