Metabolic activation of flunitrazepam via nitroreduction mediated by aldo-keto reductase 1C3.

ABSTRACT: Aldo-keto reductases (AKRs) are a superfamily of NAD(P)(H)-dependent oxidoreductases (phase I enzymes) that reduce aldehydes and ketones to primary and secondary alcohols, respectively. Four percent of xenobiotic biotransformation has been attributed to AKRs, although this is likely an underestimate because this is based on their ability to act as carbonyl reductases. AKRs also have an emerging role in nitroreduction. We screened 6 nitro-containing drugs (flunitrazepam, clonazepam, nimesulide, nilutamide, flutamide, and chloramphenicol) as substrates against recombinant human AKR1C1, AKR1C2, AKR1C3, and AKR1C4, using discontinuous enzymatic assays. AKR1C3 was able to reduce flunitrazepam to 7-amino-flunitrazepam. Metabolites formed during the reaction were identified by tandem mass spectro

SUBMITTER: Marques CF 

PROVIDER: S-EPMC12562546 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature