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 receptors potential as a new drug target. Despite the execution of many biological assays, to date, no bioactivity could be found for auxarthonoside (2)
NCBI PubMed ID: 26287693Publication DOI: 10.1055/s-0035-1545979Journal NLM ID: 0066751Publisher: George Thieme
Correspondence: g.koenig
uni-bonn.de
Institutions: Institute for Pharmaceutical Biology, University of Bonn, Bonn, Germany, Pharma Center Bonn, Pharmaceutical Institute, Pharmaceutical Chemistry I, University of Bonn, Bonn, Germany, Pamukkale University, Biomedical Engineering, Denizli, Turkey
Methods: 13C NMR, 1H NMR, NMR-2D, IR, biological assays, HPLC, UV, extraction, optical rotation measurement, cell growth, HR-ESI-MS, sonication, VLC
Found