J Pharmacol Pharmacother | Volume 1, Issue 1 | Research Article | Open Access
Shazia Dawood1 and Abdulla A-B Badawy2*
1Pharmacy and Allied Health Sciences, Iqra University, Pakistan
2Formerly School of Health Sciences, Cardiff Metropolitan University, UK
*Correspondance to: Abdulla A-B Badawy
Fulltext PDFFICZ (6-formylindolo[3,2-b]carbazole), a photooxidation product and a metabolite of the essential amino acid L-tryptophan (Trp), is one of the strongest ligands of the aryl hydrocarbon receptor (AhR), binding to which activates the receptor to exert profound effects on body homeostasis, including immune function. FICZ is an effective antagonist of diseases in experimental models and thus a potential drug target. We hypothesise that it may act in inflammatory conditions, bacterial infections and the associated multi-drug resistance, and cancer by immunosuppression via proinflammatory kynurenine metabolites following induction of the extrahepatic Trp-degrading enzyme indoleamine 2,3-dioxygenase (IDO). We explored by molecular docking in silico the likely interaction of FICZ with relevant enzymes of the kynurenine pathway and of NAD+ synthesis and utilisation that may underpin its potential therapeutic actions. We demonstrate the ability of FICZ to dock in silico to IDO, other enzymes of the kynurenine pathway and enzymes of NAD+ synthesis and utilisation. We suggest that FICZ influences Trp metabolism both directly and indirectly via AhR activation and other effects on proinflammatory cytokines. We propose also for the first time that FICZ may be involved in the phototherapy of neonatal hyperbilirubinemia by counteracting bilirubin toxicity. In the light of our docking results, we outline potential future studies of the effects of FICZ on Trp metabolism in relation to the above and other conditions.
Bacterial resistance; Cancer; Immune suppression; Inflammatory disease; Molecular docking; Neonatal jaundice; Tryptophan metabolism
Dawood S, A-B Badawy A. Molecular Docking of FICZ (6-Formylindolo[3,2-b]carbazole) to Kynurenine Pathway Enzymes: Biological Basis of a Potential Drug. J Pharmacol Pharm. 2024; 1(1): 1004..