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Australian Journal of Chemistry Australian Journal of Chemistry Society
An international journal for chemical science
RESEARCH ARTICLE

Cytotoxicity In Vitro, Apoptosis, Cellular Uptake, Cell Cycle Distribution, Mitochondrial Membrane Potential Detection, DNA Binding, and Photocleavage of Ruthenium(ii) Complexes

Gan-Jian Lin A , Zheng-Zheng Li A , Jun-Hua Yao B , Hong-Liang Huang C D , Yang-Yin Xie A and Yun-Jun Liu A D
+ Author Affiliations
- Author Affiliations

A School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, China.

B Instrument Analysis and Research Center, Sun Yat-Sen Uiversity, Guangzhou, 510275, China.

C School of Life Science and Biopharmaceutical, Guangdong Pharmaceutical University, Guangzhou, 510006, China.

D Corresponding authors. Email: hhongliang@163.com; lyjche@163.com

Australian Journal of Chemistry 66(5) 555-563 https://doi.org/10.1071/CH12564
Submitted: 7 November 2012  Accepted: 7 January 2013   Published: 5 February 2013

Abstract

Four new ruthenium(ii) complexes [Ru(bpy)2(NHPIP)](ClO4)2 (Ru-1), [Ru(phen)2(NHPIP)](ClO4)2 (Ru-2), [Ru(bpy)2(AHPIP)](ClO4)2 (Ru-3), and [Ru(phen)2(AHPIP)](ClO4)2 (Ru-4) (bpy = 2,2′-bipyridine; phen = 1,10-phenanthroline; NHPIP = 2-(3-nitro-4-hydroxylphenyl)imidazo[4,5-f][1,10]phenanthroline; AHPIP = 2-(3-amino-4-hydroxylphenyl)imidazo[4,5-f][1,10]phenanthroline) were synthesized and characterized by elemental analysis, electrospray mass spectrometry, and 1H NMR spectroscopy. The cytotoxicity in vitro of these complexes against BEL-7402, HeLa, MG-63, and MCF-7 cells was evaluated by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) method. Ru-4 shows the highest cytotoxic activity towards the selected cell lines among the four complexes. The morphological apoptosis was assayed by an acridine orange/ethidium bromide staining method, and the percentages of necrotic and apoptotic cells were determined by flow cytometry. The cellular uptake and the cell cycle arrest in BEL-7402 cell was investigated. The results showed these complexes inhibit the proliferation of BEL-7402 cells at G0/G1 phase arrest. The detection of mitochondrial membrane potentials using the fluorescence probe JC-1 (5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolcarbocyanine iodide) exhibited that the mitochondrial membrane potentials decrease. Upon irradiation, these complexes can effectively cleave pBR322 DNA.


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