Gold(I) complexes of water-soluble diphos-type ligands: synthesis, anticancer activity, apoptosis and thioredoxin reductase inhibition |
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Authors: | Wetzel Corinna Kunz Peter C Kassack Matthias U Hamacher Alexandra Böhler Philip Watjen Wim Ott Ingo Rubbiani Riccardo Spingler Bernhard |
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Institution: | Institut für Anorganische Chemie und Strukturchemie, Lehrstuhl I: Bioanorganische Chemie und Katalyse, Heinrich-Heine-University Düsseldorf, Universit?tsstr. 1, D-40225, Düsseldorf, Germany. |
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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. |
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