The hop-derived compounds xanthohumol,isoxanthohumol and 8-prenylnaringenin are tight-binding inhibitors of human aldo-keto reductases 1B1 and 1B10 |
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| Authors: | Jan Moritz Seliger Livia Misuri Edmund Maser Jan Hintzpeter |
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| Institution: | 1. Institute of Toxicology and Pharmacology for Natural Scientists, University Medical School Schleswig-Holstein, Kiel, Germany;2. Department of Biology, Tuscany Region PhD School in Biochemistry and Molecular Biology, University of Pisa, Pisa, Italy |
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| Abstract: | Xanthohumol (XN), a prenylated chalcone unique to hops (Humulus lupulus) and two derived prenylflavanones, isoxanthohumol (IX) and 8-prenylnaringenin (8-PN) gained increasing attention as potential anti-diabetic and cancer preventive compounds. Two enzymes of the aldo-keto reductase (AKR) superfamily are notable pharmacological targets in cancer therapy (AKR1B10) and in the treatment of diabetic complications (AKR1B1). Our results show that XN, IX and 8-PN are potent uncompetitive, tight-binding inhibitors of human aldose reductase AKR1B1 (Ki?=?15.08?μM, 0.34?μM, 0.71?μM) and of human AKR1B10 (Ki?=?20.11?μM, 2.25?μM, 1.95?μM). The activity of the related enzyme AKR1A1 was left unaffected by all three compounds. This is the first time these three substances have been tested on AKRs. The results of this study may provide a basis for further quantitative structure–activity relationship models and promising scaffolds for future anti-diabetic or carcinopreventive drugs. |
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| Keywords: | Xanthohumol 8-prenylnaringenin aldo-keto reductases diabetes tight-binding inhibition |
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