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Communication

Design, Synthesis and Cellular Characterization of a Dual Inhibitor of 5-Lipoxygenase and Soluble Epoxide Hydrolase

1
Institute of Pharmaceutical Chemistry, Goethe-University of Frankfurt, Max-von-Laue Str. 9, D-60438 Frankfurt am Main, Germany
2
Institute of Pharmaceutical Biology, Goethe-University of Frankfurt, Max-von-Laue Str. 9, D-60438 Frankfurt am Main, Germany
3
Institute of Clinical Pharmacology, Goethe-University of Frankfurt, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany
*
Authors to whom correspondence should be addressed.
Academic Editor: Cornelis J. Van der Schyf
Molecules 2017, 22(1), 45; https://doi.org/10.3390/molecules22010045
Received: 7 November 2016 / Revised: 15 December 2016 / Accepted: 23 December 2016 / Published: 29 December 2016
(This article belongs to the Special Issue Polypharmacology and Multitarget Drug Discovery)
The arachidonic acid cascade is a key player in inflammation, and numerous well-established drugs interfere with this pathway. Previous studies have suggested that simultaneous inhibition of 5-lipoxygenase (5-LO) and soluble epoxide hydrolase (sEH) results in synergistic anti-inflammatory effects. In this study, a novel prototype of a dual 5-LO/sEH inhibitor KM55 was rationally designed and synthesized. KM55 was evaluated in enzyme activity assays with recombinant enzymes. Furthermore, activity of KM55 in human whole blood and endothelial cells was investigated. KM55 potently inhibited both enzymes in vitro and attenuated the formation of leukotrienes in human whole blood. KM55 was also tested in a cell function-based assay. The compound significantly inhibited the LPS-induced adhesion of leukocytes to endothelial cells by blocking leukocyte activation. View Full-Text
Keywords: soluble epoxide hydrolase; 5-lipoxygenase; inflammation; designed multitarget ligands; leukocyte-endothelial cell interaction soluble epoxide hydrolase; 5-lipoxygenase; inflammation; designed multitarget ligands; leukocyte-endothelial cell interaction
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MDPI and ACS Style

Meirer, K.; Glatzel, D.; Kretschmer, S.; Wittmann, S.K.; Hartmann, M.; Blöcher, R.; Angioni, C.; Geisslinger, G.; Steinhilber, D.; Hofmann, B.; Fürst, R.; Proschak, E. Design, Synthesis and Cellular Characterization of a Dual Inhibitor of 5-Lipoxygenase and Soluble Epoxide Hydrolase. Molecules 2017, 22, 45. https://doi.org/10.3390/molecules22010045

AMA Style

Meirer K, Glatzel D, Kretschmer S, Wittmann SK, Hartmann M, Blöcher R, Angioni C, Geisslinger G, Steinhilber D, Hofmann B, Fürst R, Proschak E. Design, Synthesis and Cellular Characterization of a Dual Inhibitor of 5-Lipoxygenase and Soluble Epoxide Hydrolase. Molecules. 2017; 22(1):45. https://doi.org/10.3390/molecules22010045

Chicago/Turabian Style

Meirer, Karin, Daniel Glatzel, Simon Kretschmer, Sandra K. Wittmann, Markus Hartmann, René Blöcher, Carlo Angioni, Gerd Geisslinger, Dieter Steinhilber, Bettina Hofmann, Robert Fürst, and Ewgenij Proschak. 2017. "Design, Synthesis and Cellular Characterization of a Dual Inhibitor of 5-Lipoxygenase and Soluble Epoxide Hydrolase" Molecules 22, no. 1: 45. https://doi.org/10.3390/molecules22010045

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