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Your search keyword '"Lin Liu"' showing total 4 results
4 results on '"Lin Liu"'

1. Design, Synthesis, and Biological Evaluation of a New Series of Biphenyl/Bibenzyl Derivatives Functioning as Dual Inhibitors of Acetylcholinesterase and Butyrylcholinesterase

Author

Bo Feng, Lin Wang, Song Wu, Hui Fu, Guanhua Du, Wang Dongmei, and Ai-Lin Liu

Subjects
0301 basic medicine, biphenyl/bibenzyl derivatives, Aché, Stereochemistry, Pharmaceutical Science, Pharmacology, Article, Analytical Chemistry, lcsh:QD241-441, 03 medical and health sciences, chemistry.chemical_compound, Structure-Activity Relationship, 0302 clinical medicine, lcsh:Organic chemistry, Alzheimer Disease, Drug Discovery, Bibenzyls, Bibenzyl, Animals, Humans, Physical and Theoretical Chemistry, IC50, Butyrylcholinesterase, Biological evaluation, Biphenyl, Organic Chemistry, Biphenyl Compounds, molecular docking, Acetylcholinesterase, language.human_language, Alzheimer’s disease, acetylcholinesterase inhibitors, butyrylcholinesterase inhibitors, Rats, Molecular Docking Simulation, 030104 developmental biology, chemistry, Design synthesis, Chemistry (miscellaneous), Drug Design, language, Molecular Medicine, Cholinesterase Inhibitors, 030217 neurology & neurosurgery
Abstract

Alzheimer's disease (AD), the most common form of dementia in adults, is a progressive neurodegenerative disorder of the brain characterized by loss of memory and steady deterioration of cognition. Here, a series of symmetrical molecules containing biphenyl/bibenzyl scaffolds (12-36) were designed, synthesized, and evaluated for their ability to inhibit both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). A biological evaluation showed that most of these biphenyl derivatives were potent AChE and BuChE inhibitors. Among them, compound 15 displayed the greatest ability to inhibit BuChE (IC50 = 0.74 µM) and was also a good AChE inhibitor (IC50 = 1.18 µM). Compound 19 was not only a potent AChE inhibitor (IC50 = 0.096 µM), but also a mild BuChE inhibitor (IC50 =1.25 µM). Overall, these results suggested that compound 19 may be a promising agent in the treatment of AD.

Published
2017

2. Evaluation of Novel Dual Acetyl- and Butyrylcholinesterase Inhibitors as Potential Anti-Alzheimer’s Disease Agents Using Pharmacophore, 3D-QSAR, and Molecular Docking Approaches

Author

Guanhua Du, Shilun Yang, Hui Fu, Song Wu, Xiaocong Pang, Lin Wang, and Ai-Lin Liu

Subjects
Models, Molecular, 0301 basic medicine, Quantitative Structure-Activity Relationship, Pharmaceutical Science, Analytical Chemistry, chemistry.chemical_compound, DL0410, 0302 clinical medicine, Drug Discovery, Butyrylcholinesterase, Molecular Structure, biology, Acetylcholinesterase, Molecular Docking Simulation, Chemistry (miscellaneous), language, Molecular Medicine, Piperidine, Pharmacophore, Alzheimer’s disease, Protein Binding, Quantitative structure–activity relationship, Aché, Stereochemistry, Article, lcsh:QD241-441, 03 medical and health sciences, lcsh:Organic chemistry, Alzheimer Disease, cholinesterase inhibitor, Humans, Physical and Theoretical Chemistry, 3D-QSAR, Cholinesterase, Binding Sites, Organic Chemistry, Rational design, molecular docking, language.human_language, High-Throughput Screening Assays, Kinetics, kinetics, 030104 developmental biology, Anti-Anxiety Agents, chemistry, biology.protein, Cholinesterase Inhibitors, 030217 neurology & neurosurgery
Abstract

DL0410, containing biphenyl and piperidine skeletons, was identified as an acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitor through high-throughput screening assays, and further studies affirmed its efficacy and safety for Alzheimer’s disease treatment. In our study, a series of novel DL0410 derivatives were evaluated for inhibitory activities towards AChE and BuChE. Among these derivatives, compounds 6-1 and 7-6 showed stronger AChE and BuChE inhibitory activities than DL0410. Then, pharmacophore modeling and three-dimensional quantitative structure activity relationship (3D-QSAR) models were performed. The R2 of AChE and BuChE 3D-QSAR models for training set were found to be 0.925 and 0.883, while that of the test set were 0.850 and 0.881, respectively. Next, molecular docking methods were utilized to explore the putative binding modes. Compounds 6-1 and 7-6 could interact with the amino acid residues in the catalytic anionic site (CAS) and peripheral anionic site (PAS) of AChE/BuChE, which was similar with DL0410. Kinetics studies also suggested that the three compounds were all mixed-types of inhibitors. In addition, compound 6-1 showed better absorption and blood brain barrier permeability. These studies provide better insight into the inhibitory behaviors of DL0410 derivatives, which is beneficial for rational design of AChE and BuChE inhibitors in the future.

Published
2017

3. Evaluation of Novel Dual Acetyl- and Butyrylcholinesterase Inhibitors as Potential Anti-Alzheimer's Disease Agents Using Pharmacophore, 3D-QSAR and Molecular Docking Approaches.

Author

Xiaocong Pang, Hui Fu, Shilun Yang, Lin Wang, Ai-Lin Liu, Song Wu, and Guan-Hua Du

Subjects
ACETYLCHOLINESTERASE inhibitors, ALZHEIMER'S disease treatment, MOLECULAR docking, ANIONS, BUTYRYLCHOLINESTERASE, CATALYSIS
Abstract

DL0410, containing biphenyl and piperidine skeletons, was identified as an acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitor through high-throughput screening assays, and further studies affirmed its efficacy and safety for Alzheimer's disease treatment. In our study, a series of novel DL0410 derivatives were evaluated for inhibitory activities towards AChE and BuChE. Among these derivatives, compounds 6-1 and 7-6 showed stronger AChE and BuChE inhibitory activities than DL0410. Then, pharmacophore modeling and three-dimensional quantitative structure activity relationship (3D-QSAR) models were performed. The R² of AChE and BuChE 3D-QSAR models for training set were found to be 0.925 and 0.883, while that of the test set were 0.850 and 0.881, respectively. Next, molecular docking methods were utilized to explore the putative binding modes. Compounds 6-1 and 7-6 could interact with the amino acid residues in the catalytic anionic site (CAS) and peripheral anionic site (PAS) of AChE/BuChE, which was similar with DL0410. Kinetics studies also suggested that the three compounds were all mixed-types of inhibitors. In addition, compound 6-1 showed better absorption and blood brain barrier permeability. These studies provide better insight into the inhibitory behaviors of DL0410 derivatives, which is beneficial for rational design of AChE and BuChE inhibitors in the future. [ABSTRACT FROM AUTHOR]

Published
2017
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4. DL0410 Ameliorates Memory and Cognitive Impairments Induced by Scopolamine via Increasing Cholinergic Neurotransmission in Mice.

Author

Wenwen Lian, Jiansong Fang, Lvjie Xu, Wei Zhou, De Kang, Wandi Xiong, Hao Jia, Ai-Lin Liu, and Guan-Hua Du

Subjects
PARASYMPATHOMIMETIC agents, BUTYRYLCHOLINESTERASE, CHOLINERGIC receptors, ACETYLCHOLINESTERASE, SCOPOLAMINE, DONEPEZIL, LABORATORY mice
Abstract

Deficiency of the cholinergic system is thought to play a vital role in cognitive impairment of dementia. DL0410 was discovered as a dual inhibitor of acetylcholinesterase (AChE) and butyrylcholinestease (BuChE), with potent efficiency in in-vitro experiments, but its in vivo effect on the cholinergic model has not been evaluated, and its action mechanism has also not been illustrated. In the present study, the capability of DL0410 in ameliorating the amnesia induced by scopolamine was investigated, and its effect on the cholinergic system in the hippocampus and its binding mode in the active site of AChE was also explored. Mice were administrated DL0410 (3 mg/kg, 10 mg/kg, and 30 mg/kg), and mice treated with donepezil were used as a positive control. The Morris water maze, escape learning task, and passive avoidance task were used as behavioral tests. The test results indicated that DL0410 could significantly improve the learning and memory impairments induced by scopolamine, with 10 mg/kg performing best. Further, DL0410 inhibited the AChE activity and increased acetylcholine (ACh) levels in a dose-dependent manner, and interacted with the active site of AChE in a similar manner as donepezil. However, no difference in the activity of BuChE was found in this study. All of the evidence indicated that its AChE inhibition is an important mechanism in the anti-amnesia effect. In conclusion, DL0410 could be an effective therapeutic drug for the treatment of dementia, especially Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Published
2017
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