Apr 20th, 1:00 PM - 4:00 PM
Investigation of the C10 Electrophilic Site in DNA Interstrand Cross-Linking by Synthetic Aziridinomitosenes
Dr. Don L. Warner
Mitomycin C (MC), a quinone-containing cancer therapy agent, is biologically active by alkylating DNA. The crosslinks prevent translation and replication, therein destroying cancer cells. While useful for treating cancer, MC’s clinical utility is limited by its high toxicity. Synthetic aziridinomitosenes, compounds structurally similar to MC, have comparable effects on cancer cells, but by an unknown mechanism. A series of aziridinomitosene analogs have been prepared to study role of the potential active sites on the molecule. Previously, significant differences in the efficacy of the aziridinomitosenes have been observed with a subtle addition of a methyl group to the C6 or C7 position. Two more analogs have been synthesized to complete the examination of active sites on the molecule, now with variation at the C10 position. DNA binding studies of these final analogs should contribute insight to the mechanism for crosslink formation.