Next Article in Journal
Solution Conformation of Heparin Tetrasaccharide. DFT Analysis of Structure and Spin–Spin Coupling Constants
Next Article in Special Issue
Ethnomedicinal, Phytochemical and Pharmacological Investigations of Perilla frutescens (L.) Britt.
Previous Article in Journal
In Vitro Evaluation of Sulforaphane and a Natural Analog as Potent Inducers of 5-Fluorouracil Anticancer Activity
Previous Article in Special Issue
Tagetes spp. Essential Oils and Other Extracts: Chemical Characterization and Biological Activity
Open AccessArticle

Selective Inhibition of Human AKR1B10 by n-Humulone, Adhumulone and Cohumulone Isolated from Humulus lupulus Extract

1
Institute of Toxicology and Pharmacology for Natural Scientists, University Medical School Schleswig-Holstein, Campus Kiel, Brunswikerstr. 10, D-24105 Kiel, Germany
2
Department of Pharmaceutical Biology, Faculty of Mathematics and Natural Sciences, Christian-Albrechts-Universität zu Kiel, Gutenbergstraße 76, D-24118 Kiel, Germany
3
Department of Pharmaceutical Chemistry, Faculty of Mathematics and Natural Sciences, Christian-Albrechts-Universität zu Kiel, Gutenbergstraße 76, D-24118 Kiel, Germany
*
Author to whom correspondence should be addressed.
Academic Editor: Marcello Locatelli
Molecules 2018, 23(11), 3041; https://doi.org/10.3390/molecules23113041
Received: 17 October 2018 / Revised: 16 November 2018 / Accepted: 19 November 2018 / Published: 21 November 2018
(This article belongs to the Special Issue Natural Product Pharmacology and Medicinal Chemistry)
Hop-derived compounds have been subjected to numerous biomedical studies investigating their impact on a wide range of pathologies. Isomerised bitter acids (isoadhumulone, isocohumulone and isohumulone) from hops, used in the brewing process of beer, are known to inhibit members of the aldo-keto-reductase superfamily. Aldo-keto-reductase 1B10 (AKR1B10) is upregulated in various types of cancer and has been reported to promote carcinogenesis. Inhibition of AKR1B10 appears to be an attractive means to specifically treat RAS-dependent malignancies. However, the closely related reductases AKR1A1 and AKR1B1, which fulfil important roles in the detoxification of endogenous and xenobiotic carbonyl compounds oftentimes crossreact with inhibitors designed to target AKR1B10. Accordingly, there is an ongoing search for selective AKR1B10 inhibitors that do not interact with endogeneous AKR1A1 and AKR1B1-driven detoxification systems. In this study, unisomerised α-acids (adhumulone, cohumulone and n-humulone) were separated and tested for their inhibitory potential on AKR1A1, AKR1B1 and AKR1B10. Also AKR1B10-mediated farnesal reduction was effectively inhibited by α-acid congeners with Ki-values ranging from 16.79 ± 1.33 µM (adhumulone) to 3.94 ± 0.33 µM (n-humulone). Overall, α-acids showed a strong inhibition with selectivity (115–137 fold) for AKR1B10. The results presented herein characterise hop-derived α-acids as a promising basis for the development of novel and selective AKR1B10-inhibitors. View Full-Text
Keywords: aldo-keto reductases; cancer; tight-binding inhibition; selective inhibition; humulone; farnesal reduction; hops; humulus lupulus; alpha-acids aldo-keto reductases; cancer; tight-binding inhibition; selective inhibition; humulone; farnesal reduction; hops; humulus lupulus; alpha-acids
Show Figures

Figure 1

MDPI and ACS Style

Seliger, J.M.; Cicek, S.S.; Witt, L.T.; Martin, H.-J.; Maser, E.; Hintzpeter, J. Selective Inhibition of Human AKR1B10 by n-Humulone, Adhumulone and Cohumulone Isolated from Humulus lupulus Extract. Molecules 2018, 23, 3041.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop