Drugs Against Neurodegenerative Diseases: Design and Synthesis of 6-Amino-substituted Imidazo[1,2-b]pyridazines as Acetylcholinesterase Inhibitors

2017 ◽  
Vol 2 (2) ◽  
pp. 842-847 ◽  
Author(s):  
P. Sridhar ◽  
Manikandan Alagumuthu ◽  
B. Ram ◽  
Sivakumar Arumugam ◽  
Sabbasani Rajasekhara Reddy
Keyword(s):  
Neurodegenerative Diseases ◽  
Acetylcholinesterase Inhibitors ◽  
Design And Synthesis

scholarly journals Thiopurine Derivative-Induced Fpg/Nei DNA Glycosylase Inhibition: Structural, Dynamic and Functional Insights

2020 ◽  
Vol 21 (6) ◽  
pp. 2058 ◽  
Author(s):  
Charlotte Rieux ◽  
Stéphane Goffinont ◽  
Franck Coste ◽  
Zahira Tber ◽  
Julien Cros ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Research Field ◽  
Inhibition Mechanism ◽  
Dna Glycosylases ◽  
Irreversible Inhibitor ◽  
Structural Dynamic ◽  
Structural Class ◽  
Design And Synthesis ◽  
Pharmacological Targets ◽  
Active Research

DNA glycosylases are emerging as relevant pharmacological targets in inflammation, cancer and neurodegenerative diseases. Consequently, the search for inhibitors of these enzymes has become a very active research field. As a continuation of previous work that showed that 2-thioxanthine (2TX) is an irreversible inhibitor of zinc finger (ZnF)-containing Fpg/Nei DNA glycosylases, we designed and synthesized a mini-library of 2TX-derivatives (TXn) and evaluated their ability to inhibit Fpg/Nei enzymes. Among forty compounds, four TXn were better inhibitors than 2TX for Fpg. Unexpectedly, but very interestingly, two dithiolated derivatives more selectively and efficiently inhibit the zincless finger (ZnLF)-containing enzymes (human and mimivirus Neil1 DNA glycosylases hNeil1 and MvNei1, respectively). By combining chemistry, biochemistry, mass spectrometry, blind and flexible docking and X-ray structure analysis, we localized new TXn binding sites on Fpg/Nei enzymes. This endeavor allowed us to decipher at the atomic level the mode of action for the best TXn inhibitors on the ZnF-containing enzymes. We discovered an original inhibition mechanism for the ZnLF-containing Fpg/Nei DNA glycosylases by disulfide cyclic trimeric forms of dithiopurines. This work paves the way for the design and synthesis of a new structural class of inhibitors for selective pharmacological targeting of hNeil1 in cancer and neurodegenerative diseases.

The design and synthesis of human branched-chain amino acid aminotransferase inhibitors for treatment of neurodegenerative diseases

2006 ◽  
Vol 16 (9) ◽  
pp. 2337-2340 ◽  
Author(s):  
Lain-Yen Hu ◽  
Peter A. Boxer ◽  
Suzanne R. Kesten ◽  
Huangshu J. Lei ◽  
David J. Wustrow ◽  
...  
Keyword(s):  
Amino Acid ◽  
Neurodegenerative Diseases ◽  
Design And Synthesis ◽  
Branched Chain Amino Acid ◽  
Branched Chain

scholarly journals Design and synthesis of new piperidone grafted acetylcholinesterase inhibitors

2017 ◽  
Vol 27 (2) ◽  
pp. 228-231 ◽  
Author(s):  
Alireza Basiri ◽  
Michelle Xiao ◽  
Alec McCarthy ◽  
Debashis Dutta ◽  
Siddappa N. Byrareddy ◽  
...  
Keyword(s):  
Acetylcholinesterase Inhibitors ◽  
Design And Synthesis

Design and synthesis of thienopyridines as novel templates for acetylcholinesterase inhibitors

2012 ◽  
Vol 22 (9) ◽  
pp. 4087-4095 ◽  
Author(s):  
Mohga M. Badran ◽  
Maha Abdel Hakeem ◽  
Suzan M. Abuel-Maaty ◽  
Afaf El-Malah ◽  
Rania M. Abdel Salam
Keyword(s):  
Acetylcholinesterase Inhibitors ◽  
Design And Synthesis

Rational design and synthesis of dihydropyrimidine based dual binding site acetylcholinesterase inhibitors

2016 ◽  
Vol 69 ◽  
pp. 91-101 ◽  
Author(s):  
Sufyan Ahmad ◽  
Fatima Iftikhar ◽  
Farhat Ullah ◽  
Abdul Sadiq ◽  
Umer Rashid
Keyword(s):  
Binding Site ◽  
Rational Design ◽  
Acetylcholinesterase Inhibitors ◽  
Design And Synthesis

scholarly journals Acetylcholinesterase Inhibitors in the Treatment of Neurodegenerative Diseases and the Role of Acetylcholinesterase in their Pathogenesis

2021 ◽  
Vol 22 (17) ◽  
pp. 9290
Author(s):  
Łucja Justyna Walczak-Nowicka ◽  
Mariola Herbet
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Response ◽  
Neurodegenerative Diseases ◽  
Acetylcholinesterase Inhibitors ◽  
New Drugs ◽  
Ache Inhibitors ◽  
Disease Entities ◽  
New Compounds ◽  
Potential Use

Acetylcholinesterase (AChE) plays an important role in the pathogenesis of neurodegenerative diseases by influencing the inflammatory response, apoptosis, oxidative stress and aggregation of pathological proteins. There is a search for new compounds that can prevent the occurrence of neurodegenerative diseases and slow down their course. The aim of this review is to present the role of AChE in the pathomechanism of neurodegenerative diseases. In addition, this review aims to reveal the benefits of using AChE inhibitors to treat these diseases. The selected new AChE inhibitors were also assessed in terms of their potential use in the described disease entities. Designing and searching for new drugs targeting AChE may in the future allow the discovery of therapies that will be effective in the treatment of neurodegenerative diseases.

Highly Significant Scaffolds to Design and Synthesis Cholinesterase Inhibitors as Anti-Alzheimer Agents

2019 ◽  
Vol 19 (19) ◽  
pp. 1577-1598 ◽  
Author(s):  
Yaghoub Pourshojaei ◽  
Khalil Eskandari ◽  
Ali Asadipour
Keyword(s):  
Cognitive Abilities ◽  
Memory Loss ◽  
Acetylcholinesterase Inhibitors ◽  
Crystallographic Structure ◽  
Design And Synthesis ◽  
Cortex Area ◽  
Wide Range ◽  
Common Term ◽  
The Brain

: Alzheimer, a progressive disease, is a common term for memory loss which interferes with daily life through severe influence on cognitive abilities. Based on the cholinergic hypothesis, and Xray crystallographic determination of the structure of acetylcholinesterase (AChE) enzyme, the level of acetylcholine (ACh, an important neurotransmitter associated with memory) in the hippocampus and cortex area of the brain has a direct effect on Alzheimer. This fact encourages scientists to design and synthesize a wide range of acetylcholinesterase inhibitors (AChEIs) to control the level of ACh in the brain, keeping in view the crystallographic structure of AChE enzyme and drugs approved by the Food and Drug Administration (FDA). : AChEIs have slightly diverse pharmacological properties, but all of them work by inhibiting the segregation of ACh by blocking AChE. We reviewed significant scaffolds introduced as AChEIs. In some studies, the activity against butyrylcholinesterase (BuChE) has been evaluated as well because BuChE is a similar enzyme to neuronal acetylcholinesterase and is capable of hydrolyzing ACh. In order to study AChEIs effectively, we divided them structurally into 12 classes and briefly explained effective AChEIs and compared their activities against AChE enzyme.

Design and synthesis of new donepezil analogs derived from arylpiperazine scaffold as acetylcholinesterase inhibitors

2020 ◽  
pp. 1-11
Author(s):  
Zafer Sahin ◽  
Sevde Nur Biltekin ◽  
Emre Fatih Bülbül ◽  
Leyla Yurttas ◽  
Barkin Berk ◽  
...  
Keyword(s):  
Acetylcholinesterase Inhibitors ◽  
Design And Synthesis
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