title: In vitro and in vivo evaluation of water-soluble iminophosphorane ruthenium(II) compounds. A potential chemotherapeutic agent for triple negative breast cancer.
abstract: A series of organometallic ruthenium(II) complexes containing iminophosphorane ligands have been synthesized and characterized. Cationic compounds with chloride as counterion are soluble in water (70-100 mg/mL). Most compounds (especially highly water-soluble 2) are more cytotoxic to a number of human cancer cell lines than cisplatin. Initial mechanistic studies indicate that the cell death type for these compounds is mainly through canonical or caspase-dependent apoptosis, nondependent on p53, and that the compounds do not interact with DNA or inhibit protease cathepsin B. In vivo experiments of 2 on MDA-MB-231 xenografts in NOD.CB17-Prkdc SCID/J mice showed an impressive tumor reduction (shrinkage) of 56% after 28 days of treatment (14 doses of 5 mg/kg every other day) with low systemic toxicity. Pharmacokinetic studies showed a quick absorption of 2 in plasma with preferential accumulation in the breast tumor tissues when compared to kidney and liver, which may explain its high efficacy in vivo.
authors.affiliation: Department of Chemistry, Brooklyn College and The Graduate Center, The City University of New York , 2900 Bedford Avenue, Brooklyn, New York 11210, United States.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Frik
authors.forename: Alberto
authors.initials: A
authors.lastname: Martínez
authors.forename: Benelita T
authors.initials: BT
authors.lastname: Elie
authors.forename: Oscar
authors.initials: O
authors.lastname: Gonzalo
authors.forename: Daniel
authors.initials: D
authors.lastname: Ramírez de Mingo
authors.forename: Mercedes
authors.initials: M
authors.lastname: Sanaú
authors.forename: Roberto
authors.initials: R
authors.lastname: Sánchez-Delgado
authors.forename: Tanmoy
authors.initials: T
authors.lastname: Sadhukha
authors.forename: Swayam
authors.initials: S
authors.lastname: Prabha
authors.forename: Joe W
authors.initials: JW
authors.lastname: Ramos
authors.forename: Isabel
authors.initials: I
authors.lastname: Marzo
authors.forename: María
authors.initials: M
authors.lastname: Contel
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use*; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D066298:In Vitro Techniques; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000627:therapeutic use*; D010753:Phosphoranes / Q000138:chemical synthesis / Q000627:therapeutic use; D012428:Ruthenium / Q000627:therapeutic use*; D012995:Solubility; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy*; D014867:Water
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D009942:Organometallic Compounds; D010753:Phosphoranes; D014867:Water; D012428:Ruthenium