A Dual-Action Gold(I) Prodrug Targeting Redox Homeostasis and Extracellular Matrix Remodeling in Ovarian Cancer

Ovarian cancer is characterized by early metastatic dissemination, frequent relapses, and limited therapeutic options following the onset of platinum resistance. To address these challenges, a dual-action gold(I) prodrug, RDL-15, was designed to concurrently interfere with intracellular redox regulation and extracellular matrix remodeling. RDL-15 combines the gold(I) pharmacophore derived from Auranofin with the scaffold of LP-158, a carboxylate-based inhibitor of gelatinases MMP-2 and MMP-9 previously described. The complex retains micromolar cytotoxic activity in ovarian cancer cell lines A2780 and SKOV-3, including the cisplatin and AF-resistant A2780/R variant, and induces an early reduction of thioredoxin reductase activity. In SKOV-3 cells, characterized by high migratory and invasive capacity, RDL-15 significantly suppresses migration and invasion, whereas Et3PAuCl alone shows no intrinsic anti-invasive effect. Computational analyses further support a structure–function relationship linking gold–ligand bonding features to the observed biological profile.