Replacement of the Thiosugar of Auranofin with Iodide Enhances the Anticancer Potency in a Mouse Model of Ovarian Cancer

• DOI: 10.1021/acsmedchemlett.9b00007
• Publication Date: 2019-02-07T18:37:10Z
• Authors: Tiziano Marzo; Lara Massai; Alessandro Pratesi; Matteo Stefanini; Damiano Cirri; Francesca Magherini; Matteo Becatti; Ida Landini; Stefania Nobili; Enrico Mini; Olivia Crociani; Annarosa Arcangeli; Serena Pillozzi; Tania Gamberi; Luigi Messori
• Keywords: 0303 health sciences; 03 medical and health sciences; Auranofin; gold compounds; ovarian cancer; metal-based drugs; in vivo orthotopic model; Auranofin, gold compounds, in vivo orthotopic model, metal-based drugs, ovarian cancer; Auranofin; gold compounds; in vivo orthotopic model; metal-based drugs; ovarian cancer; 3. Good health

In recent years, a few successful attempts were made to repurpose the clinically approved antiarthritic gold drug, Auranofin (AF), as an anticancer agent. The present study shows that the iodido(triethylphosphine)gold(I) complex, (Et 3 PAuI hereafter)-an AF analogue where the thiosugar ligand is simply replaced by one iodide ligand-manifests a solution chemistry resembling that of AF and exerts similar cytotoxic and proapoptotic effects on A2780 human ovarian cancer cells in vitro. However, when evaluated in a preclinical orthotopic model of ovarian cancer, Et 3 PAuI produces a far superior anticancer action than AF inducing a nearly complete tumor remission. The highly promising in vivo performances here documented for Et 3 PAuI warrant its further evaluation as a drug candidate for ovarian cancer treatment.