Inorganic Chemistry Department, Faculty of Chemistry, University of Bucharest, 23 Dumbrava Rosie Street, 050107 Bucharest, Romania.
Eur J Med Chem. 2010 Apr;45(4):1627-34. doi: 10.1016/j.ejmech.2009.12.015. Epub 2010 Jan 22.
Synthesis and biological activity investigation of complex compounds of Cu(II) are challenging issues because of the metal is not a xenobiotic one and the activity of ligands could be modulated by complexation. Complex combinations of Cu(II) and Pd(II) with thiosemicarbazone derivatives of 2-hydroxy-8-R-tricyclo[7.3.1.0.(2,7)]tridecane-13-one (where R=C(3)H(7), C(4)H(3)O) were synthesized. The characterization of the ligands and the newly formed compounds was done by (1)H NMR, (13)C NMR, UV-vis, IR, ESR spectroscopy, elemental analysis, molar electric conductibility and thermal studies. Experiments performed to identify the structures proved that the ligands coordinate to metal ions in different ways - neutral bidentate or mononegative bidentate. Also, if copper(II) acetate, copper(II) nitrate, copper(II) chloride and copper(II) thiocyanate were used, the ligands coordinated in a mononegative bidentate fashion. If copper(II) sulfate was used, the ligands coordinated in a neutral bidentate fashion. The biological activity for the copper(II) synthesized compounds was assessed in terms of antibacterial or antiproliferative activity. The antibacterial activity of the complexes against Staphylococcus aureus var. Oxford 6538, Escherichia coli ATCC 10536, Klebsielle pneumoniae ATCC 100131 and Candida albicans ATCC 10231 strains was studied and compared with that of free ligands. The effect of complex compounds on the proliferation of HeLa cells was tested. For all tested complexes an antiproliferative activity was noted at concentrations higher than 1 microM, but lower than 10 microM. Therefore, complex compounds of copper(II) were synthesized, structurally characterized and tested for biological activity, proving both antibacterial and antiproliferative activity.
合成和研究铜(II)配合物的生物活性是一个具有挑战性的问题,因为金属不是异源生物,配体的活性可以通过配合物来调节。合成了 2-羟基-8-R-三环[7.3.1.0.(2,7)]十三烷-13-酮(其中 R=C(3)H(7), C(4)H(3)O)的硫代半卡巴腙衍生物与铜(II)和钯(II)的复杂组合。通过(1)H NMR、(13)C NMR、UV-vis、IR、ESR 光谱、元素分析、摩尔电导率和热研究对配体和新形成的化合物进行了表征。为了确定结构而进行的实验证明,配体以不同的方式与金属离子配位 - 中性双齿或单负双齿。此外,如果使用醋酸铜、硝酸铜、氯化铜和硫氰酸铜,配体以单负双齿方式配位。如果使用硫酸铜,配体以中性双齿方式配位。评估了合成铜(II)化合物的生物活性,包括抗菌或抗增殖活性。研究了配合物对金黄色葡萄球菌 var. Oxford 6538、大肠杆菌 ATCC 10536、肺炎克雷伯菌 ATCC 100131 和白色念珠菌 ATCC 10231 菌株的抗菌活性,并与游离配体进行了比较。测试了配合物对 HeLa 细胞增殖的影响。对于所有测试的配合物,在高于 1 microM 但低于 10 microM 的浓度下都观察到抗增殖活性。因此,合成了铜(II)配合物,对其进行了结构表征,并测试了其生物活性,证明了它们具有抗菌和抗增殖活性。