Finding More Efficient Ways to Treat Cancer Patients
Human carbonyl reductase (HCBR) is known to catalyze the NADPH-dependent reduction of a wide variety of carbonyl compounds. Anthracyclines, used to treat cancer, are reduced by HCBR and the resulting metabolites are implicated in the cardiotoxicity associated with anthracycline therapy. Many compounds have been discovered to bind and thus inhibit HCBR. These compounds have similar structures to the nitriles: 3-Phenoxyphalonitrile, 4-Phenoxyphalonitrile, and 4-Phenoxybenzonitrile. The nitriles are different to recently discovered inhibitors of HCBR because they have cyano groups bonded to different locations on the benzene rings. Kenetic studies were used to determine whether the nitriles were effective as inhibitors. The nearly identical kcat values show that the studied nitriles that we tested are ineffective at inhibiting HCBR.