Apr 20th, 1:00 PM - 4:00 PM
Synthesis of Fluorescently Labeled Aziridinomitosenes to Study the Cellular Fate of Potential Cancer Therapy Agents
Dr. Don L. Warner
Mitomycin C (MC) is a clinically administered cancer therapy agent that forms interstrand crosslinks with DNA, arresting cell replication. However, the utility of MC is limited by adverse side effects present in the course of treatment. Incentive towards an alternative drug with reduced side effects and increased potency has led to the synthesis of many analogous compounds. Among these analogs are a group of compounds called Aziridinomitosenes (AZMs) that are structurally similar to MC and may potentially offer significant improvements. We have proposed that AZMs possess a mechanistic advantage over MC which involves a nucleophilic attack to activate the molecule prior to DNA alkylation, whereas MC requires reductive activation. It is within the aims of this research to investigate the cytoxicity of relevant AZMs in cancer cell lines. This includes experiments that investigate the cellular fate of AZMs using optical microscopy and fluorescent labels, explicitly focusing on DNA as the target. Synthesis of appropriate AZMs labeled with fluorescent tags is currently underway. The results of these studies will help clarify the mechanism for AZM DNA alkylation and the interactions of AZMs within human cancer cells.