The hop-derived compounds xanthohumol, isoxanthohumol and 8-prenylnaringenin are tight-binding inhibitors of human aldo-keto reductases 1B1 and 1B10

Journal of Enzyme Inhibition and Medicinal Chemistry

Livia Misuri¹  Jan Moritz Seliger²  Jan Hintzpeter²  Edmund Maser² 

[1] Department of Biology, Tuscany Region PhD School in Biochemistry and Molecular Biology, University of Pisa, Pisa, Ital;Institute of Toxicology and Pharmacology for Natural Scientists, University Medical School Schleswig-Holstein, Kiel, Germany;

关键词: Xanthohumol;    8-prenylnaringenin;    aldo-keto reductases;    diabetes;    tight-binding inhibition;   

DOI  :  10.1080/14756366.2018.1437728

来源: publisher

【 摘 要 】

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.

【 授权许可】

CC BY