title: Synthesis and anticancer activity of carbosilane metallodendrimers based on arene ruthenium(ii) complexes.
abstract: A series of new organometallic carbosilane dendrimers (first and second generation) and the corresponding non-dendritic mononuclear based on ruthenium arene fragments are described. The metallodendrimers were prepared by reactions of the precursor [Ru(η(6)-p-cymene)Cl2]2 with carbosilane dendrimers functionalized with N-donor monodentate ligands such as NH2- and pyridine, or with N,O-, N,N-chelating imine ligands. While the dendrimer precursors are insoluble in DMSO or water, novel metallodendrimers are soluble in DMSO and some of them are even highly soluble in water. The molecular structure of the "Ru-NH2" mononuclear compound (zero generation) was determined by single-crystal X-ray crystallography. The cytotoxicity activity of these dendritic structures was evaluated in several human cancer cell lines and compared with that of the corresponding mononuclear ruthenium complexes. Most compounds display significant cytotoxic activities in the low micromolar range with the first generation ruthenium dendrimers being the most active compounds. The cell death type for selected compounds has been studied as well as their reactivity towards relevant biomolecules such as DNA, Human Serum Albumin (HSA) and Cathepsin-B. All the data point to a mode of action different from that of cisplatin for most complexes. First generation ruthenium dendrimers inhibit Cathepsin-B, which may suggest potential antimetastatic properties of these compounds.
authors.affiliation: Departamento de Química Orgánica y Química Inorgánica, Universidad de Alcalá, Campus Universitario, E-28871 Alcalá de Henares, Spain. javier.delamata@uah.es and Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Maroto-Díaz
authors.affiliation: Department of Chemistry, Brooklyn College and The Graduate Center, The City University of New York, Brooklyn, New York 11210, USA. mariacontel@brooklyn.cuny.edu and Biology PhD Program, The Graduate Center, The City University of New York, 365 Fifth Avenue, New York, NY 10016, USA.
authors.forename: Benelita T
authors.initials: BT
authors.lastname: Elie
authors.affiliation: Departamento de Química Orgánica y Química Inorgánica, Universidad de Alcalá, Campus Universitario, E-28871 Alcalá de Henares, Spain. javier.delamata@uah.es.
authors.forename: Pilar
authors.initials: P
authors.lastname: Gómez-Sal
authors.affiliation: Departamento de Biomedicina y Biotecnología, Universidad de Alcalá, Campus Universitario, E-28871 Alcalá de Henares, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Pérez-Serrano
authors.affiliation: Departamento de Química Orgánica y Química Inorgánica, Universidad de Alcalá, Campus Universitario, E-28871 Alcalá de Henares, Spain. javier.delamata@uah.es and Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Gómez
authors.affiliation: Department of Chemistry, Brooklyn College and The Graduate Center, The City University of New York, Brooklyn, New York 11210, USA. mariacontel@brooklyn.cuny.edu and Biology PhD Program, The Graduate Center, The City University of New York, 365 Fifth Avenue, New York, NY 10016, USA.
authors.forename: María
authors.initials: M
authors.lastname: Contel
authors.affiliation: Departamento de Química Orgánica y Química Inorgánica, Universidad de Alcalá, Campus Universitario, E-28871 Alcalá de Henares, Spain. javier.delamata@uah.es and Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Spain.
authors.forename: F
authors.initials: F
authors.lastname: Javier de la Mata
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D002401:Cathepsin B / Q000037:antagonists & inhibitors; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D060326:Chemistry Techniques, Synthetic; D004247:DNA / Q000378:metabolism; D050091:Dendrimers / Q000737:chemistry*; D006801:Humans; D008024:Ligands; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D012428:Ruthenium / Q000737:chemistry*; D012709:Serum Albumin / Q000378:metabolism; D012821:Silanes / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D050091:Dendrimers; D008024:Ligands; D009942:Organometallic Compounds; D012709:Serum Albumin; D012821:Silanes; C504072:carbosilane; D012428:Ruthenium; D004247:DNA; D002401:Cathepsin B