title: Ru(III) anticancer agents with aromatic and non-aromatic dithiocarbamates as ligands: Loading into nanocarriers and preliminary biological studies.
abstract: Since the discovery of cisplatin in the 1960s, other metal complexes have been investigated as potential antitumor agents to overcome the side-effects associated with the administration of the Pt-based drug. In line with our previous research, in this work we report the synthesis and characterization of mono- and dinuclear Ru(III) complexes with the pyrrolidinedithiocarbamate (PDT) ligand and the more sterically-hindered carbazole-dithiocarbamato ligand (CDT), to compare their properties (both at the chemical and antiproliferative level), in an attempt to assess a structure-activity rationale. Moreover, to overcome the scarce solubility under physiological conditions of the Ru(III)-dithiocarbamato compounds, the biocompatible copolymer Pluronic® F127 has been used, to encapsulate the metal derivatives in water-soluble micellar carriers. Finally, preliminary biological evaluations on CDT and PDT compounds along with their nanoformulations, open intriguing perspectives in anticancer chemotherapy. In particular, comparing the structure of the Ru(III) derivatives, the ionic dinuclear PDT complex shows an important cytotoxic action in comparison to its neutral counterparts. Moreover, the micellar carrier improves the overall activity of the encapsulated Ru(III)-PDT chemotherapeutics. On the other hand, the nanoformulation of the CDT derivatives allows us to solubilize both the 1:3 and the 2:5 complexes and to state their inactivity.
authors.affiliation: Department of Chemical Sciences, University of Padova, Via F. Marzolo 1, 35131 Padova, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Scintilla
authors.affiliation: Department of Chemical Sciences, University of Padova, Via F. Marzolo 1, 35131 Padova, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Brustolin
authors.affiliation: Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, Via Giustiniani, 2, 35128 Padova, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Gambalunga
authors.affiliation: Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, Via Giustiniani, 2, 35128 Padova, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Chiara
authors.affiliation: Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, Via Giustiniani, 2, 35128 Padova, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Trevisan
authors.affiliation: Department of Chemical Sciences, University of Padova, Via F. Marzolo 1, 35131 Padova, Italy. Electronic address: chiara.nardon@unipd.it.
authors.forename: C
authors.initials: C
authors.lastname: Nardon
authors.affiliation: Department of Chemical Sciences, University of Padova, Via F. Marzolo 1, 35131 Padova, Italy. Electronic address: dolores.fregona@unipd.it.
authors.forename: D
authors.initials: D
authors.lastname: Fregona
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D002227:Carbazoles / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D011759:Pyrrolidines / Q000737:chemistry / Q000494:pharmacology; D012428:Ruthenium / Q000737:chemistry / Q000494:pharmacology; D013859:Thiocarbamates / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D002227:Carbazoles; D004337:Drug Carriers; D011759:Pyrrolidines; D013859:Thiocarbamates; C041514:carbazole; C020972:pyrrolidine dithiocarbamic acid; D012428:Ruthenium
keywords: Cancer; Dithiocarbamate; Micelle; Nanoformulation; Pluronic F127; Ru(III) complexes