Ru(CO)x-Core complexes with benzimidazole ligands: synthesis, X-ray structure and evaluation of anticancer activity in vivo
| Autor: | Bernhard K. Keppler, Luigi Messori, Michael A. Jakupec, Antonello Merlino, Federica Scaletti, Walter Berger, Renzo Cini, Gabriella Tamasi, Anton A. Legin, Petra Heffeter |
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| Přispěvatelé: | Tamasi, Gabriella, Merlino, Antonello, Scaletti, Federica, Heffeter, Petra, Legin, Anton A, Jakupec, Michael A, Berger, Walter, Messori, Luigi, Keppler, Bernhard K, Cini, Renzo |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Benzimidazole
biology 010405 organic chemistry Chemistry Cytochrome c 010402 general chemistry Bovine pancreatic ribonuclease 01 natural sciences Chloride Dissociation (chemistry) 0104 chemical sciences Inorganic Chemistry Crystallography chemistry.chemical_compound medicine biology.protein Density functional theory Mother liquor Conformational isomerism medicine.drug |
| Popis: | 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-[Ru(II)(CO)3Cl2L], L = MBI (2) or DMBI (4). Crystals of cis,trans-[Ru(II)(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. |
| Databáze: | OpenAIRE |
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