Anticancer activities of emetine prodrugs that are proteolytically activated by the prostate specific antigen (PSA) and evaluation of in vivo toxicity of emetine derivatives.

Emetine is a small molecule protein synthesis inhibitor that is toxic to all cell types and therefore suitable for complete killing of all types of heterogeneous cancer cells within a tumor. It becomes significantly inactive (non-toxic) when derivatized at its N-2' secondary amine. This provides a strategy for targeting emetine to cancerous tumor without killing normal cells.

Design, synthesis, and evaluation of pH-dependent hydrolyzable emetine analogues as treatment for prostate cancer.

The N-2' position of the natural product emetine has been derivatized to thiourea, urea, sulfonamide, dithiocarbamate, carbamate, and pH responsive hydrolyzable amide analogues. In vitro studies of these analogues in PC3 and LNCaP prostate cancer cell lines showed that the analogues are generally less cytotoxic (average IC(50) ranging from 0.079 to 10 μM) than emetine (IC(50) ranging from 0.