Fig. 1.

Azo reduction by gut microbiota. (A) Pathways of azo-bonded drug activation by bacterial azoreductase activity. DHQ is produced via cyclization of an intermediate of OPN501 and celecoxib-5-ASA prodrug following intramolecular lactamization (Ruiz et al., 2011). (B) Description of downstream metabolites of bacterial azo reduction and the mechanisms of action in IBD and CRC. References for each molecular function described in this subfigure: 5-ASA (Mahida et al., 1991; Cominelli et al., 1992; Rachmilewitz et al., 1992), prednisolone (Cohen et al., 2000), celecoxib (Wu et al., 2003, ; Wu et al., 2010; Gustafsson et al., 2010), sulfapyridine (Nielsen, 1982), and DHQ (Ruiz et al., 2011). (C) Presence of azoreductase-containing bacteria is required for prodrug activation in the IBD gut and CRC gut (left). Many azo-reducing bacteria have been characterized; however, some species have shown experimental evidence of azo-reduction without the full characterization of the genes responsible for azo reduction (right).