Next Article in Journal
Anti-Proliferation Activity of a Decapeptide from Perinereies aibuhitensis toward Human Lung Cancer H1299 Cells
Next Article in Special Issue
A New Sesquiterpenoid Aminoquinone from an Indonesian Marine Sponge
Previous Article in Journal
Briarenones A‒C, New Briarellin Diterpenoids from the Gorgonian Briareum violaceum
Previous Article in Special Issue
Chemical Diversity and Biological Activities of Marine Sponges of the Genus Suberea: A Systematic Review
Article Menu
Issue 2 (February) cover image

Export Article

Open AccessArticle

9-Methylfascaplysin Is a More Potent Aβ Aggregation Inhibitor than the Marine-Derived Alkaloid, Fascaplysin, and Produces Nanomolar Neuroprotective Effects in SH-SY5Y Cells

Ningbo Key Laboratory of Behavioral Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo 315211, China
Li Dak Sum Yip Yio Chin Kenneth Li Marine Biopharmaceutical Research Center, College of Food and Pharmaceutical Sciences, Ningbo University, Ningbo 315211, China
Key Laboratory of Industrial Fermentation Microbiology of Education, State Key Laboratory of Food Nutrition and Safety, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China
School of Materials Science and Chemical Engineering, Ningbo University, Ningbo 315211, China
Authors to whom correspondence should be addressed.
These authors contribute equally.
Mar. Drugs 2019, 17(2), 121;
Received: 11 January 2019 / Revised: 2 February 2019 / Accepted: 7 February 2019 / Published: 18 February 2019
(This article belongs to the Special Issue Bioactive Compounds from Marine Sponges)
PDF [2786 KB, uploaded 18 February 2019]
  |     |  


β-Amyloid (Aβ) is regarded as an important pathogenic target for Alzheimer’s disease (AD), the most prevalent neurodegenerative disease. Aβ can assemble into oligomers and fibrils, and produce neurotoxicity. Therefore, Aβ aggregation inhibitors may have anti-AD therapeutic efficacies. It was found, here, that the marine-derived alkaloid, fascaplysin, inhibits Aβ fibrillization in vitro. Moreover, the new analogue, 9-methylfascaplysin, was designed and synthesized from 5-methyltryptamine. Interestingly, 9-methylfascaplysin is a more potent inhibitor of Aβ fibril formation than fascaplysin. Incubation of 9-methylfascaplysin with Aβ directly reduced Aβ oligomer formation. Molecular dynamics simulations revealed that 9-methylfascaplysin might interact with negatively charged residues of Aβ42 with polar binding energy. Hydrogen bonds and π–π interactions between the key amino acid residues of Aβ42 and 9-methylfascaplysin were also suggested. Most importantly, compared with the typical Aβ oligomer, Aβ modified by nanomolar 9-methylfascaplysin produced less neuronal toxicity in SH-SY5Y cells. 9-Methylfascaplysin appears to be one of the most potent marine-derived compounds that produces anti-Aβ neuroprotective effects. Given previous reports that fascaplysin inhibits acetylcholinesterase and induces P-glycoprotein, the current study results suggest that fascaplysin derivatives can be developed as novel anti-AD drugs that possibly act via inhibition of Aβ aggregation along with other target mechanisms. View Full-Text
Keywords: fascaplysin; Alzheimer’s disease; Aβ; oligomer; β-carboline fascaplysin; Alzheimer’s disease; ; oligomer; β-carboline

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material


Share & Cite This Article

MDPI and ACS Style

Sun, Q.; Liu, F.; Sang, J.; Lin, M.; Ma, J.; Xiao, X.; Yan, S.; Naman, C.B.; Wang, N.; He, S.; Yan, X.; Cui, W.; Liang, H. 9-Methylfascaplysin Is a More Potent Aβ Aggregation Inhibitor than the Marine-Derived Alkaloid, Fascaplysin, and Produces Nanomolar Neuroprotective Effects in SH-SY5Y Cells. Mar. Drugs 2019, 17, 121.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Mar. Drugs EISSN 1660-3397 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top