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 [L₂Au]X (X = Cl, PF₆) are obtained. The ligands used are diphosphanes with azoyl substituents R₂P(CH₂)₂PR₂ {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(CH₂)₂PRPh {R = 1-methylimidazol-2-yl (3)} and R₂P(CH₂)₃PR₂ {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)₂Au]PF₆ and [(5)₂Au]PF₆ 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.