Cyclophosphamide is an alkylating agent that is effective against a variety of
human cancers, including
advanced prostate cancer. Due to its limited selectivity against tumor cells, cyclophosphamide is associated with serious systemic side effects. In order to develop anticancer agents with high tumor-specificity, two novel series of cyclophosphamide prodrugs were designed, synthesized and evaluated incorporating tumor-specific activation mechanisms. The first series, 4-nitrophenylcyclophosphamides, were designed to be activated by E. coli nitroreducase (NTR), an enzyme that has been used in antibody-directed and gene-directed enzyme prodrug therapy (ADEPT and GDEPT). Among the analogs…
