Anticancer Potency Studies of Coordination Driven Self-Assembled Arene-Ru-Based Metalla-Bowls

• Published in: Chembiochem : a European journal of chemical biology Vol. 15; no. 5; pp. 695 - 700
• Main Authors: Mishra, Anurag, Jeong, Yong Joon, Jo, Jae-Ho, Kang, Se Chan, Lah, Myoung Soo, Chi, Ki-Whan
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 21.03.2014; WILEY‐VCH Verlag; Wiley Subscription Services, Inc
• Subjects: anticancer activity; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; arene-Ru; biological activity; cancer; Cell growth; Cell Line, Tumor; Cell Proliferation - drug effects; Colorectal cancer; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - genetics; coordination-driven self-assembly; Gene Expression Regulation, Neoplastic - drug effects; Humans; Medical research; metalla-bowls; Models, Molecular; Molecular Conformation; Monoterpenes - chemistry; Monoterpenes - pharmacology; Neoplasms - drug therapy; Neoplasms - genetics; Organometallic Compounds - chemistry; Organometallic Compounds - pharmacology; Pyridines - chemistry; Pyridines - pharmacology; Ruthenium - chemistry; Ruthenium - pharmacology
• ISSN: 1439-4227; 1439-7633
• DOI: 10.1002/cbic.201300688

New tetranuclear cationic metalla‐bowls 5–7 with the general formula [Ru4(p‐cymene)4(N∩N)2(OO∩OO)2]4+ (N∩N=2,6‐bis(N‐(4‐pyridyl carbamoyl)pyridine, OO∩OO=2,5‐dihydroxy‐1,4‐benzoquinonato (5), OO∩OO=5,8‐dioxydo‐1,4‐naphthaquinonato (6), OO∩OO=hoxonato (7)) were prepared by the reaction of the respective dinuclear ruthenium complexes 2–4 with a bispyridine amide donor ligand 1 in methanol in the presence of AgO3SCF3.These new molecular metalla‐bowls were fully characterized by analytical techniques including elemental analysis as well as 1H and 13C NMR and HR‐ESI‐MS spectroscopy. The structure of metalla‐bowl 6 was determined from X‐ray crystal diffraction data. A UV/visible study was also carried out for the entire suite of new complexes. As with recent studies of similar arene–Ru complexes, the inhibition of cell growth by metalla‐bowls was established against SK‐hep‐1 (liver cancer), AGS (gastric cancer), and HCT‐15 (colorectal cancer) human cancer cell lines. Inhibition of cell growth by 6 was found to be considerably stronger against all cancer cell lines than the anticancer drugs, doxorubicin and cisplatin. In particular, in colorectal cancer cells, expression of the cancer suppressor genes APC and p53 was increased following exposure to 6. DIY metallic crockery: Self‐assembled metalla‐bowls were synthesized by self‐assembly of a bispyridine amide ligand and different lengths of arene–ruthenium acceptors. The structure of one was determined by X‐ray diffraction, and the cytotoxicities of all were determined against HCT‐15, SK‐hep‐1, and AGS cell lines. One was found to be considerably more potent than the reference drugs cisplatin and doxorubicin.