Luminescent Ruthenium Complexes for Theranostic Applications

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• 作者：Carolina R. Cardoso ; M谩rcia V. S. Lima ; Juliana Cheleski ; Erica J. Peterson ; Tiago Ven芒ncio ; Nicholas P. Farrell ; Rose M. Carlos
• 刊名：Journal of Medicinal Chemistry
• 出版年：2014
• 出版时间：June 12, 2014
• 年：2014
• 卷：57
• 期：11
• 页码：4906-4915
• 全文大小：434K
• 年卷期：v.57,no.11(June 12, 2014)
• ISSN：1520-4804

文摘

The water-soluble and visible luminescent complexes cis-[Ru(L-L)₂(L)₂]²⁺ where L-L = 2,2-bipyridine and 1,10-phenanthroline and L= imidazole, 1-methylimidazole, and histamine have been synthesized and characterized by spectroscopic techniques. Spectroscopic (circular dichroism, saturation transfer difference NMR, and diffusion ordered spectroscopy NMR) and isothermal titration calorimetry studies indicate binding of cis-[Ru(phen)₂(ImH)₂]²⁺ and human serum albumin occurs via noncovalent interactions with K_b = 9.8 脳 10⁴ mol^鈥? L, 螖H = 鈭?1.5 卤 0.1 kcal mol^鈥?, and T螖S = 鈭?.46 卤 0.3 kcal mol^鈥?. High uptake of the complex into HCT116 cells was detected by luminescent confocal microscopy. Cytotoxicity of cis-[Ru(phen)₂(ImH)₂]²⁺ against proliferation of HCT116p53^+/+ and HCT116p53^{鈥?鈥?/sup> shows IC₅₀ values of 0.1 and 0.7 渭mol L鈥?. Flow cytometry and western blot indicate RuphenImH mediates cell cycle arrest in the G1 phase in both cells and is more prominent in p53+/+. The complex activates proapoptotic PARP in p53鈥?鈥?/sup>, but not in p53+/+. A cytostatic mechanism based on quantification of the number of cells during the time period of incubation is suggested.}