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A new melatonin analogue 6-hydroxy- N -acetyl-β-oxotryptamine ( 1 ) was isolated from the marine-derived fungus Penicillium sp. KMM 4672. It is the second case of melatonin-related compounds isolation from microfilamentous fungi. The neuroprotective activities of this metabolite, as well as 3-methylorsellinic acid ( 2) and 8-methoxy-3,5-dimethylisochroman-6-ol ( 3 ) from Penicillium sp. KMM 4672, candidusin A ( 4 ) and 4″-dehydroxycandidusin A ( 5 ) from Aspergillus sp. KMM 4676, and diketopiperazine mactanamide ( 6 ) from Aspergillus flocculosus , were investigated in the 6-hydroxydopamine (6-OHDA)- and paraquat (PQ)-induced Parkinson's disease (PD) cell models. All of them protected Neuro2a cells against the damaging influence of 6-OHDA to varying degrees. This effect may be realized via a reactive oxygen species (ROS) scavenging pathway. The new melatonin analogue more effectively protected Neuro2A cells against the 6-OHDA-induced neuronal death, in comparison with melatonin, as well as against the PQ-induced neurotoxicity. Dehydroxylation at C-3″ and C-4″ significantly increased free radical scavenging and neuroprotective activity of candidusin-related p -terphenyl polyketides in both the 6-OHDA- and PQ-induced PD models.

Neuroprotective Activity of Some Marine Fungal Metabolites in the 6-Hydroxydopamin- and Paraquat-Induced Parkinson’s Disease Models