α-Synuclein Binding Alkaloids from the Australian Bryozoan Amathia tricornis

In this study, we conducted the first chemical investigation of the Australian bryozoan Amathia tricornis, leading to the isolation and characterization of 11 new metabolites, including the bromoindoles tricornamines A−E (1−5), phenethylamine amathamines E−F (6−7), and guanadino-containing phenethylamides tricornamides A−D (8−11), together with three known compounds; amathamides E−F (12−13) and lamourimidazolinium trifluoroacetate (14). We also report the binding affinity of 6, 7, 9 and 10 to the Parkinson’s disease implicated protein α-synuclein. This has provided new insight into the structure−activity relationships of brominated phenethylamino metabolites towards this neurodegenerative disease-relevant target. The new natural products expand the chemical diversity reported from Amathia species and further support bryozoans as a promising source of unique compounds.