title: Gold(I) complexes of water-soluble diphos-type ligands: synthesis, anticancer activity, apoptosis and thioredoxin reductase inhibition.
abstract: Gold(I) complexes of imidazole and thiazole-based diphos type ligands were prepared and their potential as chemotherapeutics investigated. Depending on the ligands employed and the reaction conditions complexes [L(AuCl)(2)] and [L(2)Au]X (X = Cl, PF(6)) are obtained. The ligands used are diphosphanes with azoyl substituents R(2)P(CH(2))(2)PR(2) {R = 1-methylimidazol-2-yl (1), 1-methylbenzimidazol-2-yl (4), thiazol-2-yl (5) and benzthiazol-2-yl (6)} as well as the novel ligands RPhP(CH(2))(2)PRPh {R = 1-methylimidazol-2-yl (3)} and R(2)P(CH(2))(3)PR(2) {R = 1-methylimidazol-2-yl (2)}. The cytotoxic activity of the complexes was assessed against three human cancer cell lines and a rat hepatoma cell line and correlated to the lipophilicity of the compounds. The tetrahedral gold complexes [(3)(2)Au]PF(6) and [(5)(2)Au]PF(6) with intermediate lipophilicity (logD(7.4) = 0.21 and 0.25) showed significant cytotoxic activity in different cell lines. Both compounds induce apoptosis and inhibit the enzymes thioredoxin reductase and glutathione reductase.
authors.affiliation: Institut für Anorganische Chemie und Strukturchemie, Lehrstuhl I: Bioanorganische Chemie und Katalyse, Heinrich-Heine-University Düsseldorf, Universitätsstr. 1, D-40225, Düsseldorf, Germany.
authors.forename: Corinna
authors.initials: C
authors.lastname: Wetzel
authors.forename: Peter C
authors.initials: PC
authors.lastname: Kunz
authors.forename: Matthias U
authors.initials: MU
authors.lastname: Kassack
authors.forename: Alexandra
authors.initials: A
authors.lastname: Hamacher
authors.forename: Philip
authors.initials: P
authors.lastname: Böhler
authors.forename: Wim
authors.initials: W
authors.lastname: Watjen
authors.forename: Ingo
authors.initials: I
authors.lastname: Ott
authors.forename: Riccardo
authors.initials: R
authors.lastname: Rubbiani
authors.forename: Bernhard
authors.initials: B
authors.lastname: Spingler
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D006801:Humans; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D050607:Organogold Compounds / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D013844:Thiazoles / Q000737:chemistry / Q000494:pharmacology; D013880:Thioredoxin-Disulfide Reductase / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D050607:Organogold Compounds; D013844:Thiazoles; C029899:imidazole; D013880:Thioredoxin-Disulfide Reductase