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一些海洋真菌代谢产物在 6-羟多巴胺和百草枯诱导的帕金森病模型中的神经保护活性。

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

机构信息

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.

Department of Marine Biotechnology, Nhatrang Institute of Technology Research and Application, Vietnam Academy of Science and Technology, 02 Hung Vuong, Nha Trang 650000, Vietnam.

出版信息

Mar Drugs. 2018 Nov 21;16(11):457. doi: 10.3390/md16110457.

DOI:10.3390/md16110457
PMID:30469376
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6265791/
Abstract

A new melatonin analogue 6-hydroxy--acetyl-β-oxotryptamine () was isolated from the marine-derived fungus 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 ( and 8-methoxy-3,5-dimethylisochroman-6-ol () from sp. KMM 4672, candidusin A () and 4″-dehydroxycandidusin A () from sp. KMM 4676, and diketopiperazine mactanamide () from , 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 -terphenyl polyketides in both the 6-OHDA- and PQ-induced PD models.

摘要

一种新的褪黑素类似物 6-羟基--乙酰-β-氧代色胺（）从海洋来源的真菌 sp. KMM 4672 中分离得到。这是从微丝真菌中分离出与褪黑素相关的化合物的第二个案例。该代谢产物的神经保护活性，以及 sp. KMM 4672 中的 3-甲基奥尔西酸（和 8-甲氧基-3,5-二甲基异苯并呋喃-6-醇（）、 sp. KMM 4676 中的 candidusin A（）和 4″-去羟基 candidusin A（），以及 sp. KMM 4676 中的 diketopiperazine mactanamide（），在 6-羟多巴胺（6-OHDA）和百草枯（PQ）诱导的帕金森病（PD）细胞模型中进行了研究。它们都在不同程度上保护 Neuro2a 细胞免受 6-OHDA 的损伤。这种作用可能是通过活性氧（ROS）清除途径实现的。与褪黑素相比，新的褪黑素类似物更有效地保护 Neuro2A 细胞免受 6-OHDA 诱导的神经元死亡，以及 PQ 诱导的神经毒性。在 6-OHDA 和 PQ 诱导的 PD 模型中，C-3″和 C-4″的去羟化显著提高了 candidusin 相关 -三联苯聚酮类化合物的自由基清除和神经保护活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8cc/6265791/6f96ecb0d1a4/marinedrugs-16-00457-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8cc/6265791/a04fc01bf01c/marinedrugs-16-00457-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8cc/6265791/384be9b17304/marinedrugs-16-00457-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8cc/6265791/7ff81c0643b3/marinedrugs-16-00457-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8cc/6265791/ea8ea70c17f2/marinedrugs-16-00457-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8cc/6265791/6f96ecb0d1a4/marinedrugs-16-00457-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8cc/6265791/a04fc01bf01c/marinedrugs-16-00457-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8cc/6265791/384be9b17304/marinedrugs-16-00457-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8cc/6265791/7ff81c0643b3/marinedrugs-16-00457-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8cc/6265791/ea8ea70c17f2/marinedrugs-16-00457-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8cc/6265791/6f96ecb0d1a4/marinedrugs-16-00457-g005.jpg

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