Naphthoquinone 12,13-Dihydro-N-methyl-6,11,13-trioxo-5Hbenzo[4,5] cyclohepta[1,2-b]naphthalen-5,12-imine (TU100) was synthesized as a potential chemotherapy agent. While testing the effects of TU100 on cancer cells, it was discovered that TU100 is an inhibitor of luciferase from both Photinus pyralis (fireflies) and Renilla reniformis (sea pansy). Luciferase produces light in these organisms using luciferin and ATP as substrates. The Km of luciferase for ATP and luciferin were found to be 80 �M and 20 �M respectively.  Subsequent assays characterized the inhibition of luciferase by TU100 with respect to both substrates.  The assays revealed that TU100 competitively inhibits with respect to luciferin and uncompetitively inhibits with respect to ATP. This new proposed mechanism of inhibition shows TU100 binding the luciferase-ATP complex, preventing subsequent action on luciferin. These results indicate TU100 as an important new compound that merits more investigation for its control of luciferase and other bioluminescent enzymes and its role as a chemotherapeutic agent.

Mechanism of luciferase inhibition by a novel naphthoquinone

243rd National Meeting (2012)

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