Azoreductases in drug metabolism

Ryan, Ali (2017) Azoreductases in drug metabolism. British Journal of Pharmacology, 174(14), pp. 2161-2173. ISSN (online) 1476-5381


Azoreductases are flavoenzymes that have been characterised in a range of prokaryotes and eukaryotes. Bacterial azoreductases are associated with the activation of two classes of drug, azo drugs for the treatment of inflammatory bowel disease and nitrofuran antibiotics. The mechanism of reduction of azo compounds is presented that requires tautomerisation of the azo compound to a quinoneimine and provides a unifying mechanism for the reduction of azo and quinone substrates by azoreductase. The importance of further work in characterisation of azoreductases from enteric bacteria is highlighted to aid in the development of novel drugs for the treatment of colon related disorders. Human azoreductases are known to play a crucial role in the metabolism of a number of quinone containing cancer chemotherapeutic drugs. The mechanism of hydride transfer to quinones, which is shared not only between eukaryotic and prokaryotic azoreductases but the wider family of NAD(P)H quinone oxidoreductases, is outlined. The importance of common SNPs in human azoreductases is described not only in cancer prognosis but also due to their effects on the efficacy of quinone drug based cancer chemotherapeutic regimens. This highlights the need to screen patients for azoreductase SNPs ahead of treatment with these regimens.

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