Inorganic and Analytical Chemistry, Department of Chemistry, University of Ioannina, 45100, Ioannina, Greece.
J Enzyme Inhib Med Chem. 2009 Jun;24(3):742-52. doi: 10.1080/14756360802361589.
Some new complexes of mefenamic acid with potentially interesting biological activity are described. The complexes of mefenamic acid [Mn(mef)(2)(H(2)O)(2)], 1, [Co(mef)(2)(H(2)O)(2)], 2, [Ni(mef)(2)(H(2)O)(2)], 3, Cu(mef)(2)(H(2)O), 4 and [Zn(mef)(2)], 5, were prepared by the reaction of mefenamic acid, a potent anti-inflammatory drug with metal salts. Optical and infrared spectral data of these new complexes are reported. Monomeric six-coordinated species were isolated in the solid state for Mn(II), Ni(II) and Co(II), dimeric five-coordinated for Cu(II) and monomeric four-coordinated for Zn(II). In DMF or CHCl(3) solution the coordination number is retained and the coordinated molecules of water are replaced by solvent molecules. The anti-oxidant properties of the complexes were evaluated using the 1,1-diphenyl-2-picrylhydrazyl, DPPH, free radical scavenging assay. The scavenging activities of the complexes were measured and compared with those of the free drug and vitamin C. We have explored their ability to inhibit soybean lipoxygenase, beta-glucuronidase and trypsin- induced proteolysis. The complex [Mn(mef)(2)(H(2)O)(2)] exhibits the highest antioxidant activity and the highest inhibitory effect against the soybean lipogygenase (LOX), properties that are not demonstrated by mefenamic acid. Their inhibitory effects on rat paw edema induced by Carrageenan was studied and compared with those of mefenamic acid. The complex [Zn(mef)(2)] exhibited a strong inhibitory effect at 0.1 mmol/Kg B.W. (81.5 +/- 1.3% inhibition), superior to the inhibition induced by mefenamic acid at the same dose (61.5 +/- 2.3% inhibition). Mefenamic acid and its metal complexes have been evaluated for antiproliferative activity in vitro against the cells of three human cancer cell lines: MCF-7 (human breast cancer cell line), T24 (bladder cancer cell line), A-549 (non-small cell lung carcinoma) and a mouse fibroblast L-929 cell line. The copper(II) complex displays against T24, MCF-7 and L-929 cancer cell lines, IC(50) values in a microM range similar to that of the antitumor drug cis-platin and they are considered for further stages of screening in vitro and/or in vivo as agents with potential antitumor activity.
描述了一些具有潜在生物活性的新型甲芬那酸配合物。通过甲芬那酸与金属盐的反应制备了甲芬那酸[Mn(mef)(2)(H(2)O)(2)]，1、[Co(mef)(2)(H(2)O)(2)]，2、[Ni(mef)(2)(H(2)O)(2)]，3、Cu(mef)(2)(H(2)O)，4 和[Zn(mef)(2)]，5 的复合物。报道了这些新配合物的光和红外光谱数据。在固态中分离出单体六配位物种，用于 Mn(II)、Ni(II)和 Co(II)，二聚体五配位用于 Cu(II)，单体四配位用于 Zn(II)。在 DMF 或 CHCl(3)溶液中，保留配位数，并用溶剂分子取代配位的水分子。使用 1,1-二苯基-2-苦基肼，DPPH，自由基清除测定法评估配合物的抗氧化特性。测量了配合物的清除活性，并与游离药物和维生素 C 进行了比较。我们研究了它们抑制大豆脂氧合酶、β-葡萄糖醛酸酶和胰蛋白酶诱导的蛋白水解的能力。配合物[Mn(mef)(2)(H(2)O)(2)]表现出最高的抗氧化活性和对大豆脂氧合酶(LOX)的最高抑制作用，这是甲芬那酸所没有的特性。研究了它们对卡拉胶诱导的大鼠足肿胀的抑制作用，并与甲芬那酸进行了比较。配合物[Zn(mef)(2)]在 0.1mmol/Kg B.W.（81.5 +/- 1.3%抑制）时表现出强烈的抑制作用，优于相同剂量下甲芬那酸诱导的抑制作用（61.5 +/- 2.3%抑制）。已经评估了甲芬那酸及其金属配合物在体外对三种人类癌细胞系：MCF-7（人乳腺癌细胞系）、T24（膀胱癌细胞系）、A-549（非小细胞肺癌）和小鼠成纤维细胞 L-929 的抗增殖活性。铜(II)配合物对 T24、MCF-7 和 L-929 癌细胞系的显示出与抗癌药物顺铂相似的 microM 范围的 IC(50)值，并且被认为是进一步的体外和/或体内筛选的候选药物，具有潜在的抗肿瘤活性。
