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

Abstract

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.

Biologically Active Echinulin-Related Indolediketopiperazines from the Marine Sediment-Derived Fungus Aspergillus niveoglaucus

“…It was recently shown that fungal metabolites may exhibit neuroprotective activities in one or both 6-OHDA-and paraquat-induced Parkinson's disease models [40]. In the present work, 4-6 showed different activity profiles in the three neurotoxin-induced cell models.…”

“…Neuroblastoma Neuro-2a line cells (1 × 10 4 cells/well) were treated with the test compounds at concentrations of 10 µM for 1 h, and then the neurotoxins at different concentrations were added to the neuroblastoma cell suspensions [40]. Rotenone (Sigma-Aldrich, USA) was used at 10 µM.…”

Marine-Derived Natural Compounds for the Treatment of Parkinson’s Disease

“…KMM 4672. These compounds could produce neuroprotective activity against 6-OHDA- and PQ-induced neuronal toxicity [27,28]. Similarly, candidusin A ( 11 ) and 4-dehydroxycandidusin A ( 12 ) from Aspergillus sp.…”

Biologically Active Metabolites from the Marine Sediment-Derived Fungus Aspergillus flocculosus

“…Fungi of the genus Aspergillus , section Circumdati ( Aspergillus insulicola , Aspergillus flocculosus , Aspergillus ochraceus , Aspergillus ochraceopetaliformis, and others) [2], are known to produce metabolites belonging to various chemical classes: aspyrone-related pentaketides [3,4], meroterpenoids [5,6], diketopiperazine alkaloids [7], drimane sesquiterpenoids and their nitrobenzoyl derivatives [8,9], steroids, and cerebrosides [10]. Many of them possess antimicrobial [4,10], antiviral [11], cytotoxic [8,11], and neuroprotective [12] activities.…”