Anthracyclines are an effective chemotherapeutic drug but have severe side effects, including cardiotoxicity and the development of resistant tumors. Thus there is much interest in modifying anthracyclines to reduce side effects and enhance efficacy. The napthoquinone abduct 12,13-Dihydro-N-methyl-6,11,13-trioxo-5H-benzo[4,5]cyclohepta[1,2-b]naphthalen-5,12-imine (TU100) was previously synthesized and showed promise as a chemotherapeutic agent. To further evaluate its structure/function relationship, various derivatives of TU100 were generated.<br/>These novel compounds were evaluated for cytotoxicity on a panel of different cancer cell lines using a resazurin-based fluorescent assay. Mechanism of cell death induction was investigated by monitoring drug induced changes in cell morphology by phase contrast microscopy over time. Effects on mitochondria were evaluated by measuring ATP production using a luciferase-based assay. Results indicate that structural alteration of TU100 functional groups alters its cytotoxicity and mechanism of action.

Biological characterization of novel napthoquinones as potential chemotherapeutics

253rd National Meeting (2017)

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