{Ru(CO)x}-Core complexes with benzimidazole ligands: synthesis, X-ray structure and evaluation of anticancer activity in vivo

• DOI: 10.1039/c6dt04295c
• Publication Date: 2017-02-16T16:53:34Z
• Authors: Gabriella Tamasi; Antonello Merlino; Federica Scaletti; Petra Heffeter; Anton A. Legin; Michael A. Jakupec; Walter Berger; Luigi Messori; Bernhard K. Keppler; Renzo Cini
• Keywords: Benzimidazole

The reaction of [Ru(CO)6Cl2], 1, with N[combining low line]3-methylbenzimidazole (MBI) and 5,6-dimethylbenzimidazole (DMBI) afforded two new complexes the general formula fac-[RuII(CO)3Cl2L], L = MBI (2) or DMBI (4). Crystals cis,trans-[RuII(CO)2Cl2(N[combining line]3-MBI)2], 3, were also obtained from mother liquor that produced 2. In presence water, dissociation Ru-N, Ru-Cl Ru-CO bonds occurred as a function time, water content pH. Density functional theory structure simulations/optimizations carried out at Becke3LYP level for evaluating relative stability possible conformers. ESI-MS studies revealed ability to link model proteins, such lysozyme, bovine pancreatic ribonuclease cytochrome c, partial release heteroaromatic base, chlorido carbonyl ligands. X-ray diffraction on crystals grown solution HEWL 2 showed removal chloride CO. Cytotoxicity tests yielded two-digit micromolar IC50 values in CH1/PA-1 SW480 cancer cells. contrast CORM-3 2, significantly reduced tumor growth was observed 4 murine colon CT-26 vivo.