Bioprecursors

• Bioprecursors result from a molecular modification of the active principle itself. This modification generates a new compound, able to be a substrate for the metabolizing enzymes (often, oxidation and reduction). The metabolite being the expected active principle.

)i (Bioactivation

• Hydroxylation of cyclophosphamide

(anticancer agent) followed by metabolite

decomposition converts the prodrug to the

cytotoxic phosphoramide mustard.

• the activation involved oxidative dealkylation followed by a spontaneous hydrolysis to the parent active nitrogen mustard.

)ii (N-dealkylation

• Diazepam is converted to the active metabolite by N-dealkylation

)iii (O-dealkylation• The analgesic phenacetin acts in the form of

its dealkylated derivative, acetaminophen

)iv (Reduction

• The non-steroidal anti-inflammatory drug sulindac is reduced in vivo to the active form

)v (Selective bioactivation

• The insecticide, Malathion (acetylcholinesterase inhibitor), is desulfurized selectively to the toxic Malaoxon, but only by insect and not mammalian enzymes, Malathion is, therefore, Relatively non-toxic to mammals.