*** IBB - CNR *** Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy. tamasi@unisi.it., Department of Chemical Sciences, University of Naples Federico II, Via Cintia, 80126, Napoli, Italy and Institute of Biostructure and Bioimaging, CNR, Via Mezzocannone 16, 80120, Napoli, Italy., Department of Chemistry, University of Florence, Via della Lastruccia 3-13, 50019 Sesto Fiorentino, Florence, Italy., Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Borschkegasse 8a, 1090 Vienna, Austria and Research Platform "Translational Cancer Therapy Research", University of Vienna, Wahringer Strasse 42, 1090 Vienna, Austria., Institute of Inorganic Chemistry, University of Vienna, Wahringer Strasse 42, 1090 Vienna, Austria. bernhard.keppler@univie.ac.at., Research Platform "Translational Cancer Therapy Research", University of Vienna, Wahringer Strasse 42, 1090 Vienna, Austria and Institute of Inorganic Chemistry, University of Vienna, Wahringer Strasse 42, 1090 Vienna, Austria. bernhard.keppler@univie.ac.at.,
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The reaction of [Ru(CO)6Cl2], 1, with N[combining low line]3-methylbenzimidazole (MBI) and 5,6-dimethylbenzimidazole (DMBI) afforded two new complexes with the general formula fac-[RuII(CO)3Cl2L], L = MBI (2) or DMBI (4). Crystals of cis,trans-[RuII(CO)2Cl2(N[combining low line]3-MBI)2], 3, were also obtained from the mother liquor that produced 2. In the presence of water, the dissociation of Ru-N, Ru-Cl and Ru-CO bonds occurred as a function of time, water content and pH. Density functional theory structure simulations/optimizations were carried out at the Becke3LYP level of theory for evaluating the relative stability of possible conformers. ESI-MS studies revealed the ability of the complexes to link model proteins, such as lysozyme, bovine pancreatic ribonuclease and cytochrome c, with the partial release of the heteroaromatic base, chlorido and carbonyl ligands. X-ray diffraction studies on crystals grown from a solution of HEWL and 2 showed the partial removal of chloride and CO. Cytotoxicity tests yielded two-digit micromolar IC50 values in CH1/PA-1 and SW480 cancer cells. In contrast to CORM-3 and 2, a significantly reduced tumor growth was observed with 4 in the murine colon cancer CT-26 model in vivo.
Petraglia F, Singh AA, Carafa V, Nebbioso A, Conte M, Scisciola L, Valente S, Baldi A, Mandoli A, Petrizzi VB, Ingenito C, De Falco S, Cicatiello V, Apicella I, Janssen-megens EM, Kim B, Yi G, Logie C, Heath S, Ruvo M, Wierenga ATJ, Flicek P, Yaspo ML, Della Valle V, Bernard O, Tomassi S, Novellino E, Feoli A, Sbardella G, Gut I, Vellenga E, Stunnenberg HG, Mai A, Martens JHA, Altucci L * Combined HAT/EZH2 modulation leads to cancer-selective cell death(58 visite) Oncotarget (ISSN: 1949-2553electronic, 1949-2553linking), 2018 May 22; 9(39): 25630-25646. Impact Factor:5.008 DettagliEsporta in BibTeXEsporta in EndNote
