GPR18 Inhibiting Amauromine and the Novel Triterpene Glycoside Auxarthonoside from the Sponge-Derived Fungus Auxarthron reticulatum.
The marine sponge-derived fungus Auxarthron reticulatum produces the cannabinoid receptor antagonist amauromine (1). Recultivation of the fungus to obtain further amounts for more detailed pharmacological evaluation of 1 additionally yielded the novel triterpene glycoside auxarthonoside (2), bearing, in nature, a rather rare sugar moiety, i.e., N-acetyl-6-methoxy-glucosamine. Amauromine (1), which inhibited cannabinoid CB1 receptors (Ki 0.178 µM) also showed antagonistic activity at the cannabinoid-like orphan receptor GPR18 (IC50 3.74 µM). The diketopiperazine 1 may thus serve as a lead structure for the development of more potent and selective GPR18 antagonists, which are required to study the orphan receptor's potential as a new drug target. Despite the execution of many biological assays, to date, no bioactivity could be found for auxarthonoside (2).
Institute for Pharmaceutical Biology, University of Bonn, Bonn, Germany.
Mamona
M
Nazir
Institute for Pharmaceutical Biology, University of Bonn, Bonn, Germany.
Henrik
H
Harms
Institute for Pharmaceutical Biology, University of Bonn, Bonn, Germany.
Irene
I
Loef
Institute for Pharmaceutical Biology, University of Bonn, Bonn, Germany.
Stefan
S
Kehraus
Institute for Pharmaceutical Biology, University of Bonn, Bonn, Germany.
Fayrouz
F
El Maddah
Pamukkale University, Biomedical Engineering, Denizli, Turkey.
Idris
I
Arslan
Pharma Center Bonn, Pharmaceutical Institute, Pharmaceutical Chemistry I, University of Bonn, Bonn, Germany.
Viktor
V
Rempel
Pharma Center Bonn, Pharmaceutical Institute, Pharmaceutical Chemistry I, University of Bonn, Bonn, Germany.
Christa E
CE
Müller
Institute for Pharmaceutical Biology, University of Bonn, Bonn, Germany.
Gabriele M
GM
König
D000470:Alkaloids / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000302:isolation & purification; D000818:Animals; D001203:Ascomycota / Q000737:chemistry*; D063387:Cannabinoid Receptor Antagonists / Q000737:chemistry* / Q000302:isolation & purification; D006027:Glycosides / Q000037:antagonists & inhibitors; D006801:Humans; D007211:Indoles / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000302:isolation & purification; D015394:Molecular Structure; D011161:Porifera / Q000382:microbiology*; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors; D043885:Receptor, Cannabinoid, CB2 / Q000037:antagonists & inhibitors; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*; D014315:Triterpenes / Q000037:antagonists & inhibitors*
D000470:Alkaloids; D063387:Cannabinoid Receptor Antagonists; C107515:GPR18 protein, human; D006027:Glycosides; D007211:Indoles; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D043562:Receptors, G-Protein-Coupled; D014315:Triterpenes; C043281:amauromine