Indoloditerpenes from a Marine-Derived Fungal Strain of <i>Dichotomomyces cejpii</i> with Antagonistic Activity at GPR18 and Cannabinoid Receptors

Abstract

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.