N-oxides as hypoxia selective cytotoxins.
N-oxide-containing compounds have been developed as prodrugs that are selectively bioactivated in the hypoxic cells in tumors. This selectivity is based on the net reduction of the N-oxide moiety in the absence of oxygen, in a one or two-electron process, by reductive enzymes. A wide range of N-oxides have been studied and some of them are currently in clinical use. This review covers the principal families of compounds under study and in clinical trials.
D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015687:Cell Hypoxia / Q000187:drug effects*; D003603:Cytotoxins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D009369:Neoplasms / Q000473:pathology; D009589:Nitrogen Oxides / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000975:Antioxidants; D003603:Cytotoxins; D009589:Nitrogen Oxides