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合成、晶体结构及 4-环己基-1-(1-(吡嗪-2-基)亚乙基)硫代缩氨基脲的锰(II)和镍(II)配合物的生物评价。

Synthesis, crystal structures, and biological evaluation of manganese(II) and nickel(II) complexes of 4-cyclohexyl-1-(1-(pyrazin-2-yl)ethylidene)thiosemicarbazide.

机构信息

Institute of Molecular and Crystal Engineering, College of Chemistry and Chemical Engineering, Henan University, Kaifeng 475004, PR China.

出版信息

Eur J Med Chem. 2011 Sep;46(9):4383-90. doi: 10.1016/j.ejmech.2011.07.009. Epub 2011 Jul 8.

Abstract

4-Cyclohexyl-1-(1-(pyrazin-2-yl)ethylidene)thiosemicarbazide (HL) and its transition metal complexes formulated as [Mn(L)(2)] (1) and [Ni(L)(2)] (2) have been prepared in 55-75% yield and characterized by elemental analysis, IR, MS, NMR and single-crystal X-ray diffraction studies. Biological activities of the synthesized compounds have been evaluated against selected Gram positive bacteria Bacillus subtilis, Gram negative bacteria Pseudomonas aeruginosa and the K562 leukemia cell line, respectively. The cytotoxicity data suggest that these compounds may be endowed with important biological properties, especially the nickel complex 2 with MIC = 31.2 μg/mL and IC(50) = 0.53 μM, respectively. Effect of the free ligand and its two complexes on Mitochondria membrane potential (MMP) and PI-associated fluorescence intensity as well as their effect on cell apoptosis in K562 leukemia cell line was also studied. The tested compounds may exert their cytotoxicity activity via induced loss of MMP.

摘要

4-环己基-1-(1-(哒嗪-2-基)亚乙基)硫代缩氨基脲(HL)及其过渡金属配合物[Mn(L) 2 ](1)和[Ni(L) 2 ](2)以 55-75%的产率合成,并通过元素分析、IR、MS、NMR 和单晶 X 射线衍射研究进行了表征。合成化合物的生物活性分别针对选定的革兰氏阳性菌枯草芽孢杆菌、革兰氏阴性菌铜绿假单胞菌和 K562 白血病细胞系进行了评估。细胞毒性数据表明,这些化合物可能具有重要的生物学特性,特别是镍配合物 2 的 MIC = 31.2 μg/mL 和 IC 50 = 0.53 μM。还研究了游离配体及其两种配合物对线粒体膜电位(MMP)和 PI 相关荧光强度的影响,以及它们对 K562 白血病细胞系细胞凋亡的影响。测试的化合物可能通过诱导 MMP 丧失来发挥其细胞毒性作用。

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