Thornton Laura, Dixit Vidya, Assad Letícia O N, Ribeiro Thales P, Queiroz Daniela D, Kellett Andrew, Casey Alan, Colleran John, Pereira Marcos D, Rochford Garret, McCann Malachy, O'Shea Denis, Dempsey Rita, McClean Siobhán, Kia Agnieszka Foltyn-Arfa, Walsh Maureen, Creaven Bernadette, Howe Orla, Devereux Michael
The Inorganic Pharmaceutical and Biomimetic Research Centre, Focas Research Institute, Dublin Institute of Technology, Camden Row, Dublin 8, Ireland; Centre of Applied Science for Health, Institute of Technology Tallaght Dublin, Tallaght, Dublin 24, Ireland.
The Inorganic Pharmaceutical and Biomimetic Research Centre, Focas Research Institute, Dublin Institute of Technology, Camden Row, Dublin 8, Ireland.
J Inorg Biochem. 2016 Jun;159:120-32. doi: 10.1016/j.jinorgbio.2016.02.024. Epub 2016 Mar 2.
The complexes [Ag2(OOC-(CH2)n-COO)] (n=1-10) (1-10) were synthesised and reacted with 1,10-phenanthroline (phen) to yield derivatives formulating as [Ag2(phen)x(OOC-(CH2)y-COO)]·zH2O (x=2 or 3; y=1-10; z=1-4) (11-20) which are highly water-soluble and photo-stable in aqueous solution. The phen derivatives 11-20 exhibit chemotherapeutic potential against Candida albicans, Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa and against cisplatin-sensitive breast (MCF-7) and resistant ovarian (SKOV-3) cancer cell lines. Cyclic voltammetric analysis and DNA binding and intercalation studies indicate that the mechanism of action of 11-20 is significantly different to that of their silver(I) dicarboxylate precursors and they do not induce DNA damage or ROS generation in mammalian cells. The representative complexes 9 and 19 (containing the undecanedioate ligand) were both found to significantly reduce superoxide and hydrogen peroxide induced oxidative stress in the yeast S. cerevisiae.
合成了配合物[Ag2(OOC-(CH2)n-COO)](n = 1 - 10)(1 - 10),并使其与1,10 - 菲咯啉(phen)反应,生成通式为[Ag2(phen)x(OOC-(CH2)y-COO)]·zH2O(x = 2或3;y = 1 - 10;z = 1 - 4)(11 - 20)的衍生物,这些衍生物在水溶液中具有高度水溶性且光稳定。酚衍生物11 - 20对白色念珠菌、大肠杆菌、金黄色葡萄球菌和铜绿假单胞菌以及对顺铂敏感的乳腺癌(MCF - 7)和耐药卵巢癌(SKOV - 3)细胞系具有化疗潜力。循环伏安分析以及DNA结合和嵌入研究表明,11 - 20的作用机制与其二羧酸银(I)前体的作用机制显著不同,并且它们不会在哺乳动物细胞中诱导DNA损伤或活性氧生成。发现代表性配合物9和19(含有十一烷二酸配体)均能显著降低酵母酿酒酵母中超氧化物和过氧化氢诱导的氧化应激。