Neuroprotective Activity of Some Marine Fungal Metabolites in the 6-Hydroxydopamin- and Paraquat-Induced Parkinson’s Disease Models
Ekaterina A. Yurchenko,
Ekaterina S. Menchinskaya,
Evgeny A. Pislyagin,
Phan Thi Hoai Trinh,
Elena V. Ivanets,
Olga F. Smetanina,
Anton N. Yurchenko
Affiliations
Ekaterina A. Yurchenko
Laboratory of Bioassays and Mechanism of Action of Biologically Active Substances, G.B. Elyakov Pacific Institute of Bioorganic Chemistry Far Eastern Branch of Russian Academy of Sciences, Vladivostok 690022, Russia
Ekaterina S. Menchinskaya
Laboratory of Bioassays and Mechanism of Action of Biologically Active Substances, G.B. Elyakov Pacific Institute of Bioorganic Chemistry Far Eastern Branch of Russian Academy of Sciences, Vladivostok 690022, Russia
Evgeny A. Pislyagin
Laboratory of Bioassays and Mechanism of Action of Biologically Active Substances, G.B. Elyakov Pacific Institute of Bioorganic Chemistry Far Eastern Branch of Russian Academy of Sciences, Vladivostok 690022, Russia
Phan Thi Hoai Trinh
Department of Marine Biotechnology, Nhatrang Institute of Technology Research and Application, Vietnam Academy of Science and Technology, 02 Hung Vuong, Nha Trang 650000, Vietnam
Elena V. Ivanets
Laboratory of Chemistry of Microbial Metabolites, G.B. Elyakov Pacific Institute of Bioorganic Chemistry Far Eastern Branch of Russian Academy of Sciences, Vladivostok 690022, Russia
Olga F. Smetanina
Laboratory of Chemistry of Microbial Metabolites, G.B. Elyakov Pacific Institute of Bioorganic Chemistry Far Eastern Branch of Russian Academy of Sciences, Vladivostok 690022, Russia
Anton N. Yurchenko
Laboratory of Chemistry of Microbial Metabolites, G.B. Elyakov Pacific Institute of Bioorganic Chemistry Far Eastern Branch of Russian Academy of Sciences, Vladivostok 690022, Russia
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.
