Potent and Selective Cytotoxic and Anti-inflammatory Gold(III) Compounds Containing Cyclometalated Phosphine Sulfide Ligands

Abstract

Four cycloaurated phosphine sulfide complexes, [Au{κ2-2-C6H4P(S)Ph2}2][AuX2] [X=Cl (2), Br (3), I (4)] and [Au{κ2-2-C6H4P(S)Ph2}2]PF6 (5), have been prepared and thoroughly characterized. The compounds were found to be stable under physiological-like conditions and showed excellent cytotoxicity against a broad range of cancer cell lines and remarkable cytotoxicity in 3D tumor spheroids. Mechanistic studies with cervical cancer (HeLa) cells indicated that the cytotoxic effects of the compounds involve the inhibition of thioredoxin reductase and induction of apoptosis through mitochondrial disruption. In vivo experiments in nude mice bearing HeLa xenografts showed that treatment with compounds..