scholarly journals First Synthesis of Racemic Trans Propargylamino-Donepezil, a Pleiotrope Agent Able to Both Inhibit AChE and MAO-B, with Potential Interest against Alzheimer’s Disease

Molecules ◽  
2020 ◽  
Vol 26 (1) ◽  
pp. 80
Author(s):  
Benjamin Guieu ◽  
Cedric Lecoutey ◽  
Rémi Legay ◽  
Audrey Davis ◽  
Jana Sopkova de Oliveira Santos ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Biological Evaluation ◽  
Biological Characterization ◽  
Mao B ◽  
Sole Agent ◽  
Structural Analogy ◽  
Inhibitory Activities

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disease towards which pleiotropic approach using Multi-Target Directed Ligands is nowadays recognized as probably convenient. Among the numerous targets which are today validated against AD, acetylcholinesterase (ACh) and Monoamine Oxidase-B (MAO-B) appear as particularly convincing, especially if displayed by a sole agent such as ladostigil, currently in clinical trial in AD. Considering these results, we wanted to take benefit of the structural analogy lying in donepezil (DPZ) and rasagiline, two indane derivatives marketed as AChE and MAO-B inhibitors, respectively, and to propose the synthesis and the preliminary in vitro biological characterization of a structural compromise between these two compounds, we called propargylaminodonepezil (PADPZ). The synthesis of racemic trans PADPZ was achieved and its biological evaluation established its inhibitory activities towards both (h)AChE (IC50 = 0.4 µM) and (h)MAO-B (IC50 = 6.4 µM).

Preparation and Biological Evaluation of Si-Substituted HA Ceramics with Controlled Composition

2007 ◽  
Vol 361-363 ◽  
pp. 1059-1062
Author(s):  
Mickael Palard ◽  
J. Combes ◽  
Eric Champion ◽  
Didier Bernache-Assollant
Keyword(s):  
Thermal Treatment ◽  
Biological Evaluation ◽  
Precipitation Process ◽  
Biological Characterization ◽  
Hydroxyapatite Ceramics

This work aimed at preparing dense and monophasic silicated hydroxyapatite ceramics over the range 0 ≤ x ≤ 1.0 mol of silicon. The synthesis of the powder via an aqueous precipitation process followed by an adapted thermal treatment showed that it was possible to obtain dense single-phased apatite ceramics containing up to 0.6 mol of silicon. The in vitro biological characterization of these materials was performed.

scholarly journals Biological Evaluation of Newly Synthesized Biaryl Guanidine Derivatives to Arrest β-Secretase Enzymatic Activity Involved in Alzheimer’s Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Sayyad Ali ◽  
Muhammad Hassham Hassan Bin Asad ◽  
Fahad Khan ◽  
Ghulam Murtaza ◽  
Albert A. Rizvanov ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Biological Evaluation ◽  
Morris Water Maze Test ◽  
Pharmacokinetic Parameters ◽  
The Novel ◽  
Object Recognition Test ◽  
Promising Target

Proteases BACE1 (β-secretases) enzymes have been recognized as a promising target associated with Alzheimer’s disease (AD). This study was carried out on the principles of molecular docking, chemical synthesis, and enzymatic inhibition of BACE1 enzymes via biaryl guanidine-based ligands. Based on virtual screening, thirteen different compounds were synthesized and subsequently evaluated via in vitro and in vivo studies. Among them, 1,3-bis(5,6-difluoropyridin-3-yl)guanidine (compound (9)) was found the most potent (IC50=97±0.91 nM) and active to arrest (99%) β-secretase enzymes (FRET assay). Furthermore, it was found to improve the novel object recognition test and Morris water maze test significantly (p<0.05). Improved pharmacokinetic parameters, viz., Log Po/w (1.76), Log S (-2.73), and better penetration to the brain (BBB permeation) with zero Lipinski violation, made it possible to hit the BACE1 as a potential therapeutic source for AD.

scholarly journals Therapeutic Potential Of Multifunctional Derivatives Of Cholinesterase Inhibitors

2020 ◽  
Vol 19 ◽  
Author(s):  
Maja Przybyłowska ◽  
Krystyna Dzierzbicka ◽  
Szymon Kowalski ◽  
Klaudia Chmielewska ◽  
Iwona Inkielewicz-Stepniak
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Therapeutic Potential ◽  
Amyloid Plaque ◽  
Β Amyloid ◽  
Derivatives Of ◽  
And Oxidative Stress ◽  
Pro Inflammatory Cytokines

: The aim of this work is review of tacrine analogues from the last three years, which were not included in the latest review work, donepezil and galantamine hybrids from 2015 and rivastigmine derivatives from 2014. In this account we summarize the efforts toward the development and characterization of non-toxic inhibitors of cholinesterases based on mentioned drugs with various interesting additional properties such as antioxidant, decreasing β-amyloid plaque aggregation, nitric oxide production, pro-inflammatory cytokines release, monoamine oxidase-B activity, cytotoxicity and oxidative stress in vitro and in animal model that classify these hybrids as potential multifunctional therapeutic agents for Alzheimer’s disease. Moreover, herein, we have described the cholinergic hypothesis, mechanisms of neurodegeneration and current pharmacotherapy of Alzheimer’s disease which is based on the restoration of cholinergic function through blocking enzymes that break down acetylcholine.

IC-P-174: In vitro characterization of [3H]-T808 (tau PET tracer) binding in human brain tissues in Alzheimer's disease

2013 ◽  
Vol 9 ◽  
pp. P101-P101
Author(s):  
Tsing-Bau Chen ◽  
Zhizhen Zeng ◽  
Patricia Miller ◽  
Stacey O'Malley ◽  
Brett Connolly ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Human Brain ◽  
In Vitro Characterization ◽  
Pet Tracer ◽  
Tau Pet ◽  
Brain Tissues

P1-290: In vitro characterization of [3H]-T808 (tau PET tracer) binding in human brain tissues of Alzheimer's disease

2013 ◽  
Vol 9 ◽  
pp. P260-P260
Author(s):  
Zhizhen Zeng ◽  
Tsing-Bau Chen ◽  
Patricia Miller ◽  
Stacey O'Malley ◽  
Brett Connolly ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Human Brain ◽  
In Vitro Characterization ◽  
Pet Tracer ◽  
Tau Pet ◽  
Brain Tissues
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