NQO1 (
NAD(P)H:quinoneoxidoreductase 1) is a reductive
enzyme that is an important activator of bioreductive
antitumor agents. NQO1 activity varies in individual
tumors but is generally higher in
tumor cells than in normal cells. NQO1 has been used as a target for
tumor specific
drug development. We investigated a series of bioreductive
benzoquinone mustard analogs as a model for NQO1 targeted individualized
cancer chemotherapy. We compared the
tumor cell growth inhibitory activity of
benzoquinone mustard analogs with sterically bulky groups of different size and placed at different positions on the
benzoquinone ring, using tumor cell lines with different levels of NQO1. We demonstrated that functional groups of different steric size could be used to produce a series of bioreductive
antitumor agents that were activated by different levels of NQO1 in
tumor cells. This series of drugs could then be used to target cells with specific levels of NQO1 for growth inhibition and to avoid damage to normal cells, like bone marrow cells, that have low levels of NQO1. This approach could be used to develop new bioreductive
antitumor agents for NQO1 targeted individualized
cancer chemotherapy.