Abu Ali Hijazi, Fares Hadeel, Darawsheh Mohanad, Rappocciolo Emilia, Akkawi Mutaz, Jaber Suhair
Department of Chemistry, Birzeit University, P.O. Box 14, West Bank, Palestine.
Department of Chemistry, Birzeit University, P.O. Box 14, West Bank, Palestine.
Eur J Med Chem. 2015 Jan 7;89:67-76. doi: 10.1016/j.ejmech.2014.10.032. Epub 2014 Oct 14.
A series of novel Zn(II) complexes [Zn2(nap)4] (1), Zn(nap)21,10-phen, [Zn(nap)22,9-dmphen] (3), [Zn(nap)2(2-ampy)2] (4), [Zn(nap)2(imid)2] (5), [Zn(nap)2(1,2-dmimid)2] (6) (nap = naproxen, 1,10-phen = 1,10-phenanthroline, 2,9-dmphen = 2,9-dimethyl-1,10-phenanthroline, 2-ampy = 2-aminopyridine, imid = imidazole, 1,2-dmimid = 1,2-dimethyl imidazole) were synthesized and characterized using IR, UV-Vis, (1)H NMR, (13)C{(1)H} NMR spectroscopy. The crystal structure of complex 3 was determined using single-crystal X-ray diffraction. In order to assess the effect of the metal ions on the anti-bacterial activity, complexes 1-6 have been screened in vitro, against (G(+)) bacteria (Staphylococcus aureus and Micrococcus luteus) and (G(-)) bacteria (Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis and Escherichia coli) using the agar well diffusion method. Complex 2 was the only complex that showed antibacterial activity against P. aeruginosa, where the complexation of the parent ligand 1,10-phenathroline enhanced significantly the activity. All the complexes showed different activity against the different bacteria, and were compared with activity of the parent ligands. The complexes were tested also for their anti-malarial activity using two methods: a semi-quantitative micro-assay and a previously self-developed quantitative in-vitro method. Both were used to study the efficiency of these complexes in inhibiting the formation of the Malaria pigment. This is considered an important target of many known anti-malarial drugs such as Chloroquine and Amodaquine. Results showed that the efficiency of complex 3 in preventing the formation of β-hematin was 75%. The efficiency of Amodiaquine as a standard drug was reported to give 92.5.
合成了一系列新型锌(II)配合物[Zn2(nap)4](1)、[Zn(nap)21,10-phen](2)、[Zn(nap)22,9-dmphen](3)、[Zn(nap)2(2-ampy)2](4)、[Zn(nap)2(imid)2](5)、[Zn(nap)2(1,2-dmimid)2](6)(nap = 萘普生,1,10-phen = 1,10-菲咯啉,2,9-dmphen = 2,9-二甲基-1,10-菲咯啉,2-ampy = 2-氨基吡啶,imid = 咪唑,1,2-dmimid = 1,2-二甲基咪唑),并通过红外光谱、紫外-可见光谱、(1)H核磁共振、(13)C{(1)H}核磁共振光谱对其进行了表征。使用单晶X射线衍射测定了配合物3的晶体结构。为了评估金属离子对抗菌活性的影响,采用琼脂孔扩散法对配合物1-6进行了体外筛选,针对革兰氏阳性(G(+))细菌(金黄色葡萄球菌和藤黄微球菌)和革兰氏阴性(G(-))细菌(肺炎克雷伯菌、铜绿假单胞菌、奇异变形杆菌和大肠杆菌)。配合物2是唯一对铜绿假单胞菌显示抗菌活性的配合物,其中母体配体1,10-菲咯啉的络合显著增强了活性。所有配合物对不同细菌表现出不同的活性,并与母体配体的活性进行了比较。还使用两种方法测试了这些配合物的抗疟活性:一种是半定量微量测定法,另一种是先前自行开发的定量体外方法。两者都用于研究这些配合物抑制疟色素形成的效率。这被认为是许多已知抗疟药物如氯喹和阿莫地喹的重要靶点。结果表明,配合物3预防β-血红素形成的效率为75%。据报道,作为标准药物的阿莫地喹的效率为92.5。