title: Anticancer potency and multidrug-resistant studies of self-assembled arene-ruthenium metallarectangles.
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, (η(6)-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 (1)H 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.
authors.affiliation: Department of Chemistry, University of Ulsan, Ulsan 680-749, Republic of Korea.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Dubey
authors.forename: Jin Wook
authors.initials: JW
authors.lastname: Min
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Koo
authors.forename: Hyunuk
authors.initials: H
authors.lastname: Kim
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Cook
authors.forename: Se Chan
authors.initials: SC
authors.lastname: Kang
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Stang
authors.forename: Ki-Whan
authors.initials: KW
authors.lastname: Chi
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D006801:Humans; D012428:Ruthenium / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D012428:Ruthenium
keywords: antitumor agents; cancer; metallarectangles; multidrug resistance; ruthenium; self-assembly