Anticancer Potency and Multidrug‐Resistant Studies of Self‐Assembled Arene–Ruthenium Metallarectangles |
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Authors: | Dr Abhishek Dubey Jin Wook Min Hyun Jung Koo Dr Hyunuk Kim Dr Timothy R Cook Prof Se Chan Kang Prof Peter J Stang Prof Ki‐Whan Chi |
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Institution: | 1. Department of Chemistry, University of Ulsan, Ulsan 680‐749 (Republic of Korea), Fax: (+82)?52‐259‐2348;2. Department of Life Science, Gachon University, Seongnam 461‐701 (Republic of Korea);3. Energy Materials and Convergence Research Department, Korea Institute of Energy Research, Daejeon 305‐343 (Republic of Korea);4. Department of Chemistry, University of Utah, Salt Lake City, Utah 84112 (USA) |
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Abstract: | A suite of three tetraruthenium metallacycles have been obtained from 2+2] self‐assemblies between N,N′‐Di‐(4‐pyridyl)‐1,4,5,8‐naphthalenetetracarbo–xydiimide ( 4 ) and one of the three dinuclear arene ruthenium clips, (η6‐p‐iPrC6H4Me)2Ru2(OO∩OO)]OTf]2 (OO∩OO=oxalate 1 , 2,5‐dioxydo‐1,4‐benzoquinonato (dobq) 2 , 5,8‐dihydroxy‐1,4‐naphthaquinonato (donq) 3 ; OTf=triflate). All complexes were isolated in good yield (>85 %) as triflate salts and were fully characterized by using 1H NMR and UV/Vis spectroscopies, and high‐resolution electrospray mass spectrometry. A single crystal of the metallarectangle 5 was suitable for X‐ray diffraction structural characterization. The biological activities of the metallacycles were determined by using 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) assays, establishing their in vitro anticancer properties. Our results show that for the AGC (gastric cancer) cell lines, the cytotoxicity of (donq)‐containing SCC 7 exceeds that of cisplatin, which was used as a control. For HCT15 (colon cancer) cell lines, the cytotoxicity is comparable to both cisplatin and doxorubicin. An in vivo hollow fiber model was used to show growth‐inhibitory activity against HCT15 and image‐based cytometry experiments indicated that 7 induced apoptosis as the mode of cell death. Complex 7 also showed significant antitumor activity for multidrug‐resistant HCT15/CLO2 cell lines, for which doxorubicin was ineffective. |
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Keywords: | antitumor agents cancer metallarectangles multidrug resistance ruthenium self‐assembly |
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