title: Synthesis and in vitro antitumor activity of water soluble sulfonate- and ester-functionalized silver(I) N-heterocyclic carbene complexes.
abstract: The novel N-heterocyclic carbene ligand precursor NaHIm(PrSO3) (sodium 3,3'-(1H-imidazole-3-ium-1,3-diyl)dipropane-1-sulfonate) and the related silver carbene complex [Na4(Im(PrSO3))2]AgCl have been synthesized and characterized. Recrystallization of the analogous [Im(AcEt)]AgCl complex allowed the development of X-ray analysis which led to achieve relevant structural information concerning this silver(I) derivative. Both sulfonate- and ester-functionalized silver(I) N-heterocyclic carbenes (NHCs) were evaluated for their antiproliferative activities in a wide panel of human cancer cells. Complex [Na4(Im(PrSO3))2]AgCl showed a significant in vitro antiproliferative activity that was correlated with its strong ability to inhibit thioredoxin reductase. The inhibition of this selenoenzyme determined an alteration of the cellular redox environment thus leading to the induction of the apoptotic cell death through the activation of the ASK-1 pathway.
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via Marzolo 5, 35131 Padova, Italy. Electronic address: valentina.gandin@unipd.it.
authors.forename: Valentina
authors.initials: V
authors.lastname: Gandin
authors.forename: Maura
authors.initials: M
authors.lastname: Pellei
authors.forename: Marika
authors.initials: M
authors.lastname: Marinelli
authors.forename: Cristina
authors.initials: C
authors.lastname: Marzano
authors.forename: Alessandro
authors.initials: A
authors.lastname: Dolmella
authors.forename: Marco
authors.initials: M
authors.lastname: Giorgetti
authors.forename: Carlo
authors.initials: C
authors.lastname: Santini
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D006573:Heterocyclic Compounds, 1-Ring / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D048848:MAP Kinase Kinase Kinase 5 / Q000378:metabolism; D008697:Methane / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010084:Oxidation-Reduction / Q000187:drug effects; D051140:Selenoproteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012834:Silver / Q000737:chemistry / Q000494:pharmacology; D012995:Solubility; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism; D014867:Water / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D006573:Heterocyclic Compounds, 1-Ring; D009363:Neoplasm Proteins; D051140:Selenoproteins; D014867:Water; C030011:carbene; D012834:Silver; D013880:Thioredoxin-Disulfide Reductase; D048848:MAP Kinase Kinase Kinase 5; C482858:MAP3K5 protein, human; D008697:Methane
keywords: Cytotoxic activity; Enzyme inhibition; N-heterocyclic carbenes (NHCs); Silver(I) complexes; X-ray