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新型取代异烟肼的氧钒(IV)配合物的 DNA 结合、抗肿瘤活性和羟基自由基清除特性。

DNA binding, antitumor activities, and hydroxyl radical scavenging properties of novel oxovanadium (IV) complexes with substituted isoniazid.

出版信息

J Biol Inorg Chem. 2013 Dec;18(8):975-84. doi: 10.1007/s00775-013-1046-9.

DOI:10.1007/s00775-013-1046-9
PMID:24077688
Abstract

Four novel oxovanadium(IV) complexes—[VO(PAHN)(phen)] (1; PAHN is 4-pyridinecarboxylic acid, 2-[(2-hydroxy)-1-naphthalenylene] hydrazide, phen is 1,10-phenanthroline), [VO(PAHN)(bpy)] (2; bpy is 2,2′-bipyridine), [VO(PAH)(phen)] (3; PAH is 4-pyridinecarboxylic acid, 2-[(2-hydroxy)-1-phenyl]methylene hydrazide), and [VO(PAH)(bpy)] (4)—have been synthesized and characterized by elemental analysis, UV–vis spectroscopy, electrospray ionization mass spectrometry, IR spectroscopy, 1H-NMR spectroscopy, and 13C-NMR spectroscopy. Their interactions with calf thymus DNA were investigated. The results suggest that these complexes bind to DNA in an intercalative mode. All four complexes exhibited highly cytotoxic activity against tumor cells (SH-SY5Y, MCF-7, and SK-N-SH), with 50 % inhibitory concentrations of the same order of magnitude as for cisplatin or of lower order of magnitude. Complex 1 exhibited the highest interaction ability and was found to be the most potent antitumor agent among the four complexes. It can cause G2/M phase arrest of the cell cycle, induces significant apoptosis in SK-N-SH cells, and displays typical morphological apoptotic characteristics. In addition, their hydroxyl radical scavenging properties have been tested, and complex 1 was the best inhibitor.

摘要

四种新型的氧钒(IV)配合物-[VO(PAHN)(phen)](1;PAHN 是 4-吡啶羧酸,2-[(2-羟基)-1-萘基]酰肼,phen 是 1,10-菲啰啉)、[VO(PAHN)(bpy)](2;bpy 是 2,2′-联吡啶)、[VO(PAH)(phen)](3;PAH 是 4-吡啶羧酸,2-[(2-羟基)-1-苯基]亚甲基酰肼)和[VO(PAH)(bpy)](4)已经通过元素分析、紫外可见光谱、电喷雾电离质谱、红外光谱、1H-NMR 光谱和 13C-NMR 光谱进行了合成和表征。研究了它们与小牛胸腺 DNA 的相互作用。结果表明,这些配合物以嵌入模式与 DNA 相互作用。四种配合物均对肿瘤细胞(SH-SY5Y、MCF-7 和 SK-N-SH)表现出高度的细胞毒性活性,其 50%抑制浓度与顺铂相当或略低。配合物 1 表现出最高的相互作用能力,是四种配合物中最有效的抗肿瘤剂。它可以引起细胞周期的 G2/M 期阻滞,诱导 SK-N-SH 细胞发生显著的细胞凋亡,并显示出典型的细胞凋亡形态特征。此外,还测试了它们的羟基自由基清除性能,配合物 1 是最好的抑制剂。

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