title: Synthesis, characterization, and antitumor activity of water-soluble (arene)ruthenium(II) derivatives of 1,3-dimethyl-4-acylpyrazolon-5-ato ligands. First example of Ru(arene)(ligand) antitumor species involving simultaneous Ru-N7(guanine) bonding and ligand intercalation to DNA.
abstract: We report on the synthesis of novel water-soluble [(arene)Ru(II)(Q)Cl] and [(arene)Ru(II)(Q)(X)]BF4 compounds (arene = p-cymene, benzene, hexamethylbenzene; HQ = 1,3-dimethyl-4-R-(C═O)-5-pyrazolone, HQ(Me), R = methyl, HQ(Ph), R = phenyl, HQ(Naph), R = naphthyl; X = H2O, 9-ethylguanine), and their in vitro antitumor activity toward the cell lines MCF7 (HTB-22, human breast adenocarcinoma), HCT116 (CCL-247, human colorectal carcinoma), A2780 (human ovarian carcinoma), A549 (CCL-185, human lung carcinoma), and U87 MG (HTB-1, human glioblastoma). The X-ray crystal structures of two complexes were determined. One of them, {chlorido-(p-cymene)-[(1,3-dimethyl-4-(1-naphthoyl)-pyrazolon-5-ato]ruthenium(II)}, was also studied with density functional theory methods and was selected for docking on a DNA octamer showing intercalation between DNA bases by the naphthyl moiety and for Ru-N7(guanine) bonding.
authors.affiliation: Department of Chemistry, Vassar College , Poughkeepsie, New York 12604-0484, United States.
authors.forename: Francesco
authors.initials: F
authors.lastname: Caruso
authors.forename: Elena
authors.initials: E
authors.lastname: Monti
authors.forename: Julian
authors.initials: J
authors.lastname: Matthews
authors.forename: Miriam
authors.initials: M
authors.lastname: Rossi
authors.forename: Marzia Bruna
authors.initials: MB
authors.lastname: Gariboldi
authors.forename: Claudio
authors.initials: C
authors.lastname: Pettinari
authors.forename: Riccardo
authors.initials: R
authors.lastname: Pettinari
authors.forename: Fabio
authors.initials: F
authors.lastname: Marchetti
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D004273:DNA, Neoplasm / Q000187:drug effects*; D006147:Guanine / Q000737:chemistry; D006801:Humans; D007364:Intercalating Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008024:Ligands; D008958:Models, Molecular; D017975:Ruthenium Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D007364:Intercalating Agents; D008024:Ligands; D017975:Ruthenium Compounds; D006147:Guanine