Triazoloacridin-6-ones as novel inhibitors of the quinone oxidoreductases NQO1 and NQO2

A range of triazoloacridin-6-ones functionalized at C5 and C8 have been synthesized and evaluated for ability to inhibit NQO1 and NQO2. The compounds were computationally docked into the active site of NQO1 and NQO2, and calculated binding affinities were compared with IC50 values for enzyme inhibition. Excellent correlation coefficients were demonstrated suggesting a predictive QSAR model for this series of structurally similar analogues. From this we have identified some of these triazoloacridin-6-ones to be the most potent NQO2 inhibitors so far reported.

A series of 5-, 8-substituted triazoloacridin-6-ones have been synthesized and biologically evaluated as novel inhibitors of the quinone oxidoreductases, NQO1 and NQO2. Molecular modeling provides insights into their structure–activity behaviour and selectivity.Figure optionsDownload as PowerPoint slide