scholarly journals 2-Aryl-3-(arylideneamino)-1,2-dihydroquinazoline-4(3H)-ones as inhibitors of cholinesterases and self-induced β-amyloid (Aβ) aggregation: biological evaluations and mechanistic insights from molecular dynamics simulations

RSC Advances ◽  
2018 ◽  
Vol 8 (14) ◽  
pp. 7818-7831 ◽  
Author(s):  
Sri Devi Sukumaran ◽  
Fadhil Lafta Faraj ◽  
Vannajan Sanghiran Lee ◽  
Rozana Othman ◽  
Michael J. C. Buckle
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Aβ Aggregation ◽  
Amyloid Aβ ◽  
Β Amyloid ◽  
Dynamics Simulations

A series of 2-aryl-3-(arylideneamino)-1,2-dihydroquinazoline-4(3H)-ones were evaluated as inhibitors of acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) and self-induced β-amyloid (Aβ) aggregation.

Behavior of β-Amyloid 1−16 at the Air−Water Interface at Varying pH by Nonlinear Spectroscopy and Molecular Dynamics Simulations

2011 ◽  
Vol 115 (23) ◽  
pp. 5873-5880 ◽  
Author(s):  
Abigail E. Miller ◽  
Poul B. Petersen ◽  
Christopher W. Hollars ◽  
Richard J. Saykally ◽  
Jan Heyda ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Nonlinear Spectroscopy ◽  
Water Interface ◽  
Air Water Interface ◽  
Β Amyloid ◽  
Dynamics Simulations

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

Marine Drugs ◽  
2019 ◽  
Vol 17 (2) ◽  
pp. 121 ◽  
Author(s):  
Qingmei Sun ◽  
Fufeng Liu ◽  
Jingcheng Sang ◽  
Miaoman Lin ◽  
Jiale Ma ◽  
...  
Keyword(s):  
Amino Acid Residues ◽  
Neuroprotective Effects ◽  
Study Results ◽  
Aβ Aggregation ◽  
Aggregation Inhibitors ◽  
Amyloid Aβ ◽  
Β Amyloid ◽  
Dynamics Simulations ◽  
Aβ Oligomer

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.

scholarly journals Molecular Dynamics Simulations of Alzheimer's β-Amyloid Protofilaments

2005 ◽  
Vol 353 (4) ◽  
pp. 804-821 ◽  
Author(s):  
Nicolae-Viorel Buchete ◽  
Robert Tycko ◽  
Gerhard Hummer
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Β Amyloid ◽  
Dynamics Simulations

scholarly journals Effects of Point Substitutions on the Structure of Toxic Alzheimer’s β-Amyloid Channels: Atomic Force Microscopy and Molecular Dynamics Simulations

Biochemistry ◽  
2012 ◽  
Vol 51 (14) ◽  
pp. 3031-3038 ◽  
Author(s):  
Laura Connelly ◽  
Hyunbum Jang ◽  
Fernando Teran Arce ◽  
Srinivasan Ramachandran ◽  
Bruce L. Kagan ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Atomic Force Microscopy ◽  
Molecular Dynamics Simulations ◽  
Force Microscopy ◽  
Atomic Force ◽  
Β Amyloid ◽  
Dynamics Simulations
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