Nitric oxide donor and mimetic molecules in cancer chemotherapy and chemoprevention

Nitric oxide (NO) has been shown in varying circumstances to be involved in mechanisms of both chemical carcinogenesis and chemoprevention. A full understanding of the basis for these contradictory effects of NO is not yet available, but drugs that deliver NO bioactivity by acting as NO donors or NO mimetics show potential in both cancer chemoprevention and chemotherapy. It is useful to understand the differences between the chemical moieties that are incorporated in such drugs to deliver NO bioactivity. The majority of these molecules depend on bioactivation in order to fully obtain their NO mimetic effects; the reliance on bioactivation provides an opportunity to localize and control the delivery of NO bioactivity. The various chemical classes of NO donor warheads and their successful incorporation into hybrid drugs and prodrugs is briefly and critically reviewed here with an emphasis on their potential utility in cancer chemoprevention and chemotherapy.