The study on reduction and antiproliferation activity of nitrobenzocyclophosphamidesin cell culture

PurposeTo make efforts to obtain potential anticancer prodrugs for gene-directed enzyme prodrug therapy using E.coli nitroreductase.MethodsThe reductive activation and antiproliferative activity in cell culture of four benzocyclophosphamides 6a-d were tested.Results6b and 6d,both with a benzylic oxygen in the phosphorinane ring para to the nitro group,showed a modest 30 fold enhanced cyctotoxicity in E. coli nitroreductase-expressing cells.ConclusionThese results suggest that compounds 6b and 6d represent a new structure protype for reduction and a lead for further modification in the development of better analogues with improved selective toxicity to be used in gene-directed enzyme prodrug therapy.