Indoloditerpenes from a marine-derived fungal strain of Dichotomomyces cejpii with antagonistic activity at GPR18 and cannabinoid receptors.
A marine-derived strain of Dichotomomyces cejpii produces the new compounds emindole SB beta-mannoside (1) and 27-O-methylasporyzin C (2), as well as the known indoloditerpenes JBIR-03 (3) and emindole SB (4). Indole derivative 1 was found to be a CB2 antagonist, while 2 was identified as the first selective GPR18 antagonist with an indole structure. Compound 4 was found to be a nonselective CB1/CB2 antagonist. The new natural indole derivatives may serve as lead structures for the development of GPR18- and CB receptor-blocking drugs.
Institute for Pharmaceutical Biology, University of Bonn , Nussallee 6, D-53115 Bonn, Germany.
Henrik
H
Harms
Viktor
V
Rempel
Stefan
S
Kehraus
Marcel
M
Kaiser
Peter
P
Hufendiek
Christa E
CE
Müller
Gabriele M
GM
König
D019390:Arrestins / Q000187:drug effects; D001203:Ascomycota / Q000737:chemistry*; D001315:Australia; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D008362:Mannosides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D008386:Marine Biology; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D043885:Receptor, Cannabinoid, CB2 / Q000037:antagonists & inhibitors*; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*; D000071557:beta-Arrestins
C000589160:27-O-methylasporyzin C; D019390:Arrestins; D004224:Diterpenes; C107515:GPR18 protein, human; D007211:Indoles; C526003:JBIR-03; D008362:Mannosides; D043885:Receptor, Cannabinoid, CB2; D043562:Receptors, G-Protein-Coupled; D000071557:beta-Arrestins; C000589159:emindole SB beta-mannoside