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五种新型8-羟基喹啉与具有疏水侧链氨基酸的钯(II)配合物:合成、表征、细胞毒性、DNA及牛血清白蛋白相互作用研究

Five novel palladium(II) complexes of 8-hydroxyquinoline and amino acids with hydrophobic side chains: synthesis, characterization, cytotoxicity, DNA- and BSA-interaction studies.

作者信息

Mohammadi Fatemeh, Mansouri-Torshizi Hassan

机构信息

Department of Chemistry, Faculty of Science, University of Sistan and Baluchestan, Zahedan, Iran.

出版信息

J Biomol Struct Dyn. 2020 Jul;38(10):3059-3073. doi: 10.1080/07391102.2019.1651219. Epub 2019 Aug 12.

Abstract

The side effects and resistance of metal-based anticancer drugs prompted us to synthesis a novel series of five Pd(II) complexes of the type [Pd(8-QO)(AA)]; where 8-QO = anion of 8-hydroxyquinoline and AA = anions of amino acids having nonpolar aliphatic side chain such as glycine (-H), alanine (-CH), valine (-CH(CH)), leucine (-CH-CH(CH)) and isoleucine (-CH(CH)CH-CH). The complexes have been characterized with the help of FT-IR, UV-Vis, one and two-dimensional H-NMR, elemental analysis and conductivity measurements. On the basis of these characterization data, a four coordinated square planar geometry for all of these complexes have been proposed. The compounds were screened for their activities against human cancer cell line, MOLT-4 and their 50% inhibition concentration were ascertained by means of MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Since four out of the five newly synthesized compounds were found to be more active than the standard anticancer drug, cisplatin, their detailed interaction with calf thymus DNA (as a target) and bovine serum albumin (BSA) (as a carrier) were also carried out by utilizing absorption spectra, fluorescence spectra and ethidium bromide displacement studies. In these experiments, several binding and thermodynamic parameters were also calculated. These results suggested that hydrogen binding and van der Waals forces play a major role in the interaction between metal complexes with CT-DNA and BSA.Communicated by Ramaswamy H. Sarma.

摘要

金属基抗癌药物的副作用和耐药性促使我们合成了一系列新型的五个[Pd(8-QO)(AA)]型钯(II)配合物;其中8-QO = 8-羟基喹啉阴离子,AA = 具有非极性脂肪族侧链的氨基酸阴离子,如甘氨酸(-H)、丙氨酸(-CH)、缬氨酸(-CH(CH))、亮氨酸(-CH-CH(CH))和异亮氨酸(-CH(CH)CH-CH)。借助傅里叶变换红外光谱(FT-IR)、紫外可见光谱(UV-Vis)、一维和二维氢核磁共振(H-NMR)、元素分析和电导率测量对配合物进行了表征。基于这些表征数据,提出了所有这些配合物的四配位平面正方形几何结构。对这些化合物针对人癌细胞系MOLT-4的活性进行了筛选,并通过MTT(3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐)测定法确定了它们的50%抑制浓度。由于新合成的五个化合物中有四个被发现比标准抗癌药物顺铂更具活性,还利用吸收光谱、荧光光谱和溴化乙锭置换研究对它们与小牛胸腺DNA(作为靶点)和牛血清白蛋白(BSA)(作为载体)的详细相互作用进行了研究。在这些实验中,还计算了几个结合和热力学参数。这些结果表明,氢键和范德华力在金属配合物与CT-DNA和BSA之间的相互作用中起主要作用。由拉马斯瓦米·H·萨尔马通讯。

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