Heydari Maryam, Moghadam Mahboube Eslami, Tarlani AliAkbar, Farhangian Hossein
Chemistry & Chemical Engineering Research Center of Iran, Tehran, Iran.
Appl Biochem Biotechnol. 2017 May;182(1):110-127. doi: 10.1007/s12010-016-2314-2. Epub 2016 Dec 8.
Imidazole ring is a known structure in many natural or synthetic drug molecules and its metal complexes can interact with DNA and do the cleavage. Hence, to study the influence of the structure and size of the ligand on biological behavior of metal complexes, two water-soluble Pd(II) complexes of phen and FIP ligands (where phen is 1,10-phenanthroline and FIP is 2-(Furan-2-yl)-1H-Imidazo[4,5-f][1, 10]phenanthroline) with the formula of Pd(phen)(FIP) and [Pd(FIP)]Cl, that were activated against chronic myelogenous leukemia cell line, K562, were selected. Also, the interaction of these anticancer Pd(II) complexes with highly polymerized calf thymus DNA was extensively studied by means of electronic absorption, fluorescence, and circular dichroism in Tris-buffer. The results showed that the binding was positive cooperation and Pd(phen)(FIP) (K = 127 M G = 1.2) exhibited higher binding constant and number of binding sites than [Pd(FIP)]Cl (K = 13 M G = 1.03) upon binding to DNA. The fluorescence data indicates that quenching effect for Pd(phen)(FIP) (K = 58 mM) was higher than [Pd(FIP)]Cl (K = 12 mM). Also, [Pd(FIP)]Cl interacts with ethidium bromide-DNA, as non-competitive inhibition, and can bind to DNA via groove binding and Pd(phen)(FIP) can intercalate in DNA. These results were confirmed by circular dichroism spectra. Docking data revealed that longer complexes have higher interaction energy and bind to DNA via groove binding. Graphical Abstract Two anticancer Pd(II) complexes of imidazole derivative have been synthesized and interacted with calf thymus DNA. Modes of binding have been studied by electronic absorption, fluorescence, and CD measurements. [Pd(FIP)]Cl can bind to DNA via groove binding while intercalation mode of binding is observed for Pd(phen)(FIP).
咪唑环是许多天然或合成药物分子中已知的结构，其金属配合物可与DNA相互作用并进行切割。因此，为了研究配体的结构和大小对金属配合物生物学行为的影响，选择了两种分子式分别为Pd(phen)(FIP)和[Pd(FIP)]Cl的菲咯啉（phen，即1,10 - 菲咯啉）和2-(呋喃 - 2 - 基)-1H - 咪唑并[4,5 - f][1,10]菲咯啉（FIP）配体的水溶性钯(II)配合物，它们对慢性粒细胞白血病细胞系K562具有活性。此外，通过电子吸收、荧光和圆二色性在Tris缓冲液中广泛研究了这些抗癌钯(II)配合物与高度聚合的小牛胸腺DNA的相互作用。结果表明，结合是正协同作用，与DNA结合时，Pd(phen)(FIP)（K = 127 M，G = 1.2）比[Pd(FIP)]Cl（K = 13 M，G = 1.03）表现出更高的结合常数和结合位点数。荧光数据表明，Pd(phen)(FIP)（K = 58 mM）的猝灭效应高于[Pd(FIP)]Cl（K = 12 mM）。此外，[Pd(FIP)]Cl与溴化乙锭 - DNA相互作用，表现为非竞争性抑制，可通过沟槽结合与DNA结合，而Pd(phen)(FIP)可插入DNA中。这些结果通过圆二色性光谱得到证实。对接数据显示，较长的配合物具有更高的相互作用能，并通过沟槽结合与DNA结合。图形摘要 合成了两种咪唑衍生物的抗癌钯(II)配合物，并与小牛胸腺DNA相互作用。通过电子吸收、荧光和CD测量研究了结合模式。[Pd(FIP)]Cl可通过沟槽结合与DNA结合，而Pd(phen)(FIP)则观察到插入结合模式。
