A marine-derived strain of Dichotomomyces cejpii produces the new compounds emindole SB β-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.
Dichotomomyces cejpii, indoloditerpene, antagonistic activity, emindole SB beta-mannoside
NCBI PubMed ID: 24471526Publication DOI: 10.1021/np400850gJournal NLM ID: 7906882Publisher: American Society of Pharmacognosy
Correspondence: Müller CE
; König GM
Institutions: Institute for Pharmaceutical Biology, University of Bonn, Bonn, Germany, Pharma Center Bonn, Pharmaceutical Institute, Pharmaceutical Chemistry I, University of Bonn, Bonn, Germany, Swiss Tropical and Public Health Institute, Basel, Switzerland, University of Basel, Basel, Switzerland
Methods: 13C NMR, 1H NMR, IR, ESI-MS, HPLC, UV, optical rotation measurement, binding assays, HR-ESI-MS, cytotoxicity assay, HMBC, COSY, NOESY, HSQC, DEPT-135, HCl hydrolysis, VLC, cAMP phosphodiesterase assay
Found