Aziridinomitosenes (AZM) are compounds with a structural backbone related to the anticancer/antibiotic mitomycin C (MC).  In order to display its cytotoxicity, MC must be reduced and maintained under hypoxic conditions, which limits its use to solid tumors.  AZMs do not have these requirements, thus offering a potential treatment for various carcinomas. Synthetic AZM analogs with alkyl substitutions at C6 and C7 have led to increased potency.  The C6-methyl analog exhibits the highest potency, with IC50 values that are 300 times more potent than MC in experiments with HeLa and HL-60 cells.  Caspase-3 studies indicate that MC induces protease activity greater than the AZMs.  Nuclear morphology experiments indicate that MC produces nuclear swelling, while C6-methyl AZM causes nuclear condensation, suggesting a different cytotoxic mechanism. Additional studies are coordinated to isolation of nuclear and mitochondrial DNA for detection of interstrand crosslinks, and investigating reactive oxygen species levels post AZM treatment.

Probing Aziridinomitosene cytotoxic effects in human carcinomas

245th National Meeting (2013)

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