scholarly journals Synthesis of new lophine–carbohydrate hybrids as cholinesterase inhibitors: cytotoxicity evaluation and molecular modeling

MedChemComm ◽  
2019 ◽  
Vol 10 (12) ◽  
pp. 2089-2101 ◽  
Author(s):  
João Paulo Bizarro Lopes ◽  
Luana Silva ◽  
Marco Antonio Ceschi ◽  
Diogo Seibert Lüdtke ◽  
Aline Rigon Zimmer ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Modeling ◽  
Cholinesterase Inhibitors

A series of selective butyrylcholinesterase inhibitors were obtained. The absence of in vitro cytotoxicity and good ADME-Tox profile make these compounds new promising prototypes for the treatment of Alzheimer's disease.

Drug Design of Inhibitors of Alzheimer’s Disease (AD): POM and DFT Analyses of Cholinesterase Inhibitory Activity of β-amino di-Carbonyl Derivatives

2019 ◽  
Vol 19 (8) ◽  
pp. 688-705
Author(s):  
Taibi Ben Hadda ◽  
Abdur Rauf ◽  
Hsaine Zgou ◽  
Fatma Sezer Senol ◽  
Ilkay Erdogan Orhan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cholinesterase Inhibitors ◽  
Metal Accumulation ◽  
Microtiter Plate ◽  
Metal Chelation ◽  
Carbonyl Derivatives ◽  
Cholinesterase Inhibitory Activity ◽  
Inhibitory Potential

Background:Since deficit of acetylcholine has been evidenced in the Alzheimer’s disease (AD) patients, cholinesterase inhibitors are currently the most specified drug category for the remediation of AD.Method:In the present study, 16 compounds (1-16) with dicarbonyl skeletons have been synthesized and tested for their inhibitory potential in vitro against AChE and BChE using ELISA microtiter plate assays at 100 μg/mL. Since metal accumulation is related to AD, the compounds were also tested for their metal-chelation capacity.Results and Conclusion:All the investigated dicarbonyl compounds exerted none or lower than 30% inhibition against both cholinesterases, whereas compounds 2, 8 and 11 showed 37, 42, 41% of inhibition towards BChE, being the most active. The highest metal-chelation capacity was observed with compound 8 (53.58 ± 2.06%). POM and DFT analyses are in good harmonization with experimental data.

Design and Microwave-Assisted Synthesis of Aza-Resveratrol Analogs with Potent Cholinesterase Inhibition

2020 ◽  
Vol 19 (8) ◽  
pp. 630-641
Author(s):  
Brunella Biscussi ◽  
Victoria Richmond ◽  
Carlos Javier Baier ◽  
Pau Arroyo Mañez ◽  
Ana Paula Murray
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Modeling ◽  
Cholinesterase Inhibitors ◽  
Natural Compounds ◽  
Acetylcholinesterase Inhibition ◽  
Cholinesterase Inhibition ◽  
Anionic Site ◽  
Microwave Assisted ◽  
Resveratrol Analogs

Background: Currently approved Alzheimer’s disease medications mainly comprise acetylcholinesterase inhibitors. Many of these inhibitors are either natural compounds or synthetic molecules inspired in natural compounds. Hybrid molecules that can interact with different target sites of the enzyme could lead to the discovery of effective multitarget drugs. Objective: To design, synthesize, and evaluate a series of new aza-resveratrol analogs as in vitro acetyl- and butyrylcholinesterase inhibitors. Methods: The synthesis is achieved by a simple and efficient microwave-assisted method, from commercially available starting materials. Compounds are designed as hybrids of an aza-stilbene nucleus (Schiff base) connected to a tertiary amine by a hydrocarbon chain of variable length, designed to interact both with the peripheric anionic site and the catalytic site of the enzyme. Results: All the derivatives inhibit both enzymes in a concentration-dependent manner, acting as moderate to potent cholinesterase inhibitors. The most potent inhibitors are compounds 12b (IC50 = 0.43 μM) and 12a (IC50 = 0.31 μM) for acetyl- and butyrylcholinesterase, respectively. Compounds 12a and 12b also exhibit significant acetylcholinesterase inhibition in SH-SY5Y human neuroblastoma cells without cytotoxic properties. Enzyme kinetic studies and molecular modeling reveal that inhibitor 12b targets both the catalytic active site and the peripheral anionic site of acetylcholinesterase what makes it able to modulate the self-induced β-amyloid aggregation. Furthermore, the molecular modeling analysis helps to assess the impact of the linker length in the inhibitory activity of this family of new cholinesterase inhibitors. Conclusion: These compounds have the potential to serve as a dual binding site inhibitor and might provide a useful template for the development of new anti-Alzheimer’s disease agents.

scholarly journals Design, synthesis, in vitro and in vivo evaluation of tacrine–cinnamic acid hybrids as multi-target acetyl- and butyrylcholinesterase inhibitors against Alzheimer's disease

RSC Advances ◽  
2017 ◽  
Vol 7 (54) ◽  
pp. 33851-33867 ◽  
Author(s):  
Yao Chen ◽  
Hongzhi Lin ◽  
Jie Zhu ◽  
Kai Gu ◽  
Qi Li ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cinnamic Acid ◽  
Cholinesterase Inhibitors ◽  
In Vivo Evaluation ◽  
Design Synthesis

A series of tacrine–cinnamic acid hybrids are synthesized as multi-target cholinesterase inhibitors against Alzheimer's disease.

scholarly journals Bis (Diamines) Cu and Zn Complexes of Flurbiprofen as Potential Cholinesterase Inhibitors: In Vitro Studies and Docking Simulations

Crystals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 208
Author(s):  
Muhammad Jamil ◽  
Nargis Sultana ◽  
Rizwan Ashraf ◽  
Maryam Bashir ◽  
Muhammad Fayyaz ur Rehman ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Magnetic Susceptibility ◽  
Metal Complexes ◽  
Single Crystal ◽  
Cholinesterase Inhibitors ◽  
Distorted Octahedral Geometry ◽  
X Ray ◽  
Docking Simulations

Alzheimer’s disease (AD) causes dementia and continuous damage to brain cells. Cholinesterase inhibitors can alleviate the condition by increasing communication between the nerve cells and reducing the risk of dementia. In an effort to treat Alzheimer’s disease, we synthesized flurbiprofen-based diamines (1,2 diaminoethane and 1,3 diaminopropane) Zn(II), Cu(II) metal complexes and characterized them by single-crystal X-ray analysis, NMR, (FT)-IR, UV-Vis, magnetic susceptibility, elemental analysis and conductivities measurements. Synthesized diamine metal complexes appeared in ionic forms and have distorted octahedral geometry based on conductivity studies, magnetic susceptibility and electronic studies. Single crystal X-ray diffraction analysis confirmed (2b) Cu(H2O)2(L1)2(L2)2 complex formation. Moreover, we tested all synthesized metal complexes against the cholinesterase enzyme that showed higher inhibition potential. In general, copper metal complexes showed higher inhibitory activities than simple metal complexes with flurbiprofen. These synthesized metal complexes may derive more effective and safe inhibitors for cholinesterases.

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