Modification of cellular DNA by synthetic aziridinomitosenes.

Bioorganic & medicinal chemistry (2015-11-07)
Chris M Mallory, Ryan P Carfi, SangPhil Moon, Kenneth A Cornell, Don L Warner
ABSTRACT

Two synthetic aziridinomitosenes (AZMs), Me-AZM and H-AZM, structurally related to mitomycin C (MC) were evaluated for their anticancer activity against six cancer cell lines (HeLa, Jurkat, T47D, HepG2, HL-60, and HuT-78) and tested for their DNA-modifying abilities in Jurkat cells. Cytotoxicity assays showed that Me-AZM is up to 72-fold and 520-fold more potent than MC and H-AZM, respectively. Me-AZM also demonstrated increased DNA modification over MC and H-AZM in alkaline COMET and Hoechst fluorescence assays that measured crosslinks in cellular DNA. Me-AZM and H-AZM treatment of Jurkat cells was found to sponsor significant DNA-protein crosslinks using a K-SDS assay. The results clearly indicate that the AZM C6/C7 substitution pattern plays an important role in drug activity and supports both DNA-DNA and DNA-protein adduct formation as mechanisms for inducing cytotoxic effects.

MATERIALS
Product Number
Brand
Product Description

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