2-crotonyloxymethyl-2-cyclohexenone and Breast-Neoplasms

Human glutathione (GSH) transferase (hGSTP1-1) catalyzes the conversion of antitumor 2-crotonyloxymethyl-2-cycloalkenones (COMCs) to highly reactive exocyclic enone alkylating agents. In vitro efficacy studies show that the cytotoxicities of the COMCs directly correlate with the level of expression of GSTP1-1 in MCF-7(piGST) versus MCF-7wt breast tumors, indicating that the exocyclic enones are the actual cytotoxic species. The COMCs are a potentially important new class of prodrugs, which can specifically target multi-drug-resistant tumors overexpressing hGSTP1-1.

Topics: Antineoplastic Agents, Alkylating; Breast Neoplasms; Cell Line, Tumor; Cyclohexanones; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Female; Glutathione S-Transferase pi; Humans; Prodrugs; Structure-Activity Relationship