Since Human
CYP1 enzymes catalyze the metabolic activation of procarcinogens and deactivation of certain anticancer drugs, the inhibition of these
enzymes has been considered as an effective approach for
chemoprevention and treatment of CYP1-mediated drug resistance. Recent knowledge relating to the enhanced expression of CYP1B1 in
tumors also provided certain advantages in
cancer therapy by the activation of
prodrugs only in
tumor cells. This review concentrates on the characterized CYP1 inhibitors and CYP1-activatied anticancer
prodrugs. The mechanism for
enzyme inhibition and activation of
prodrugs, the
cancer preventive/therapeutic potential of these chemicals and their related SARs are highlighted. According to their structural features, CYP1 inhibitors are divided into the following categories:
flavonoids, trans-
stilbenes,
coumarins,
terpenoids,
alkaloids,
quinones,
isothiocyanates and synthetic aromatics. In the same way, CYP1-activatied
prodrugs are categorized into four groups:
benzothiazoles,
flavonoids,
stilbenes and
alkylating agents. Almost all of these inhibitors and
prodrugs are planar molecules with one aromatic ring and some have similarity with identified CYP1 substrates. CYP1 inhibitors could effectively block the procarcinogen-induced
tumor initiation in animal models and benefit us with
chemoprevention. The advent of
Phortress and
aminoflavone as clinical candidates shows promising perspectives in developing CYP1-mediated
prodrugs as chemotherapeutic drugs that are specifically activated in
tumors. All of these preclinical and clinical studies indicate that inhibitors and
prodrugs target CYP1 are promising anticancer strategies.