fluoxetine-conjugated platinum(IV) prodrugs

Fluoxetine-conjugated platinum(IV) prodrugs are a class of dual-action chemotherapeutic agents designed to overcome multidrug resistance in cancer therapy, particularly for triple-negative breast cancer (TNBC). These compounds are synthesized by covalently linking the selective serotonin reuptake inhibitor (SSRI) and eukaryotic elongation factor-2 kinase (eEF2K) inhibitor fluoxetine to a platinum(IV)-based scaffold derived from cisplatin or oxaliplatin. The resulting "two-in-one" prodrugs combine the DNA-damaging cytotoxicity of platinum drugs with the chemosensitizing and eEF2K-inhibitory effects of fluoxetine. Lead compounds such as monosubstituted 8 and disubstituted 12 have demonstrated dramatically increased cytotoxicity compared to cisplatin in TNBC cell lines by promoting DNA damage-induced apoptosis and autophagy via eEF2K inhibition. These agents also downregulate key drug resistance proteins (P-gp, GST-π, ATM, RAD51), inhibit tumor growth and metastasis in animal models with reduced toxicity versus cisplatin alone, and stimulate antitumor immune responses including T-cell proliferation and Th1 cytokine production[1][2][9].

Other names

fluoxetine–Pt(IV) prodrugfluoxetine–cisplatin(IV) conjugatefluoxetine–oxaliplatin(IV) conjugate