scholarly journals Cyanobiphenyls: novel H3 receptor ligands with cholinesterase and MAO B inhibitory activity as multitarget compounds for potential treatment of Alzheimer’s disease

2021 ◽  
pp. 105129
Author(s):  
Justyna Godyń ◽  
Paula Zaręba ◽  
Dorota Łażewska ◽  
Dorota Stary ◽  
David Reiner-Link ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Inhibitory Activity ◽  
Potential Treatment ◽  
Receptor Ligands ◽  
Mao B ◽  
H3 Receptor

Rational design of new multitarget histamine H3 receptor ligands as potential candidates for treatment of Alzheimer’s disease

2020 ◽  
Vol 207 ◽  
pp. 112743
Author(s):  
Dorota Łażewska ◽  
Marek Bajda ◽  
Maria Kaleta ◽  
Paula Zaręba ◽  
Agata Doroz-Płonka ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Rational Design ◽  
Receptor Ligands ◽  
Histamine H3 Receptor ◽  
H3 Receptor ◽  
Histamine H3

Search for new multi-target compounds against Alzheimer’s disease among histamine H3 receptor ligands

2020 ◽  
Vol 185 ◽  
pp. 111785 ◽  
Author(s):  
Marek Bajda ◽  
Dorota Łażewska ◽  
Justyna Godyń ◽  
Paula Zaręba ◽  
Kamil Kuder ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Receptor Ligands ◽  
Histamine H3 Receptor ◽  
H3 Receptor ◽  
Histamine H3

Development of Phthalimide-Donepezil Hybrids as Potent Multitarget- Directed Ligands for the Treatment of Alzheimer’s Disease

2020 ◽  
Vol 17 (9) ◽  
pp. 1155-1163
Author(s):  
Lintao Yu ◽  
Jian Shi ◽  
Xinfeng Cheng ◽  
Keren Wang ◽  
Shuang Liu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Inhibitory Activity ◽  
Biological Activities ◽  
Docking Study ◽  
Binding Mode ◽  
Mao B ◽  
Ic50 Value ◽  
Ache Inhibitory Activity

Background: Due to the complex etiology of AD, multi-target-directed ligands (MTDLs), combining two or more distinct pharmacological moieties, have been developed in both symptomatic and disease-modifying efficiencies and are considered as an effective way for the treatment of AD. Methods: To test their biological activities, including AChE/BChE inhibitory activity and MAOA/ MAO-B inhibitory activity. In addition, molecular modeling studies were performed to afford insight into the binding mode. Results: The results displayed that compound 4c showed the best AChE inhibitory activity with an IC50 value of 4.2 μM, which was supported by the kinetic study and docking study. Compound 4c was also a selective MAO-B inhibitor (IC50 = 8.2 μM). Moreover, compound 4c could cross the blood-brain barrier in vitro. Conclusion: Compound 4c deserved to further study as a potential multifunctional agent for the treatment of Alzheimer’s disease.

Identify Compounds' Target Against Alzheimer's Disease Based on In-Silico Approach

2019 ◽  
Vol 16 (3) ◽  
pp. 193-208 ◽  
Author(s):  
Yan Hu ◽  
Guangya Zhou ◽  
Chi Zhang ◽  
Mengying Zhang ◽  
Qin Chen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Small Molecule ◽  
Characteristic Curve ◽  
Machine Learning Algorithms ◽  
Learner Model ◽  
Mao B ◽  
Number Of Patients ◽  
Sar Model ◽  
Set Up

Background: Alzheimer's disease swept every corner of the globe and the number of patients worldwide has been rising. At present, there are as many as 30 million people with Alzheimer's disease in the world, and it is expected to exceed 80 million people by 2050. Consequently, the study of Alzheimer’s drugs has become one of the most popular medical topics. Methods: In this study, in order to build a predicting model for Alzheimer’s drugs and targets, the attribute discriminators CfsSubsetEval, ConsistencySubsetEval and FilteredSubsetEval are combined with search methods such as BestFirst, GeneticSearch and Greedystepwise to filter the molecular descriptors. Then the machine learning algorithms such as BayesNet, SVM, KNN and C4.5 are used to construct the 2D-Structure Activity Relationship(2D-SAR) model. Its modeling results are utilized for Receiver Operating Characteristic curve(ROC) analysis. Results: The prediction rates of correctness using Randomforest for AChE, BChE, MAO-B, BACE1, Tau protein and Non-inhibitor are 77.0%, 79.1%, 100.0%, 94.2%, 93.2% and 94.9%, respectively, which are overwhelming as compared to those of BayesNet, BP, SVM, KNN, AdaBoost and C4.5. Conclusion: In this paper, we conclude that Random Forest is the best learner model for the prediction of Alzheimer’s drugs and targets. Besides, we set up an online server to predict whether a small molecule is the inhibitor of Alzheimer's target at http://47.106.158.30:8080/AD/. Furthermore, it can distinguish the target protein of a small molecule.

scholarly journals Volatile terpenoids as potential drug leads in Alzheimer’s disease

2017 ◽  
Vol 15 (1) ◽  
pp. 332-343 ◽  
Author(s):  
Karolina A. Wojtunik-Kulesza ◽  
Katarzyna Targowska-Duda ◽  
Katarzyna Klimek ◽  
Grażyna Ginalska ◽  
Krzysztof Jóźwiak ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mtt Assay ◽  
Inhibitory Activity ◽  
Biological Activities ◽  
Plant Metabolites ◽  
Secondary Plant Metabolites ◽  
Docking Simulations ◽  
Ache Inhibitory Activity ◽  
Volatile Terpenoids

AbstractAlzheimer’s disease (AD) is by far the most prevalent of all known forms of dementia. Despite wide-spread research, the main causes of emergence and development of AD have not been fully recognized. Natural, low-molecular, lipophilic terpenoids constitute an interesting group of secondary plant metabolites, that exert biological activities of possible use in the prevention and treatment of AD. In order to identify secondary metabolites possessing both antioxidant activity and the potential to increase the level of acetylcholine, selected terpenoids have been screened for possible acetylcholinesterase inhibitory activity by use of two methods, namely Marston (chromatographic assay) and Ellman (spectrophotometric assay). In order to describe the interaction between terpenes and AChE active gorge, molecular docking simulations were performed. Additionally, all analyzed terpenes were also evaluated for their cytotoxic properties against two normal cell lines using MTT assay. The obtained results show that: carvone (6), pulegone (8) and γ-terpinene (7) possess desirable AChE inhibitory activity. MTT assay revealed low or lack of cytotoxicity of these metabolites. Thus, among the investigated terpenes, carvone (6), pulegone (8) and y-terpinene (7) can be recognized as compounds with most promising activities in the development of multi-target directed ligands.

Novel 3-phenylcoumarin–lipoic acid conjugates as multi-functional agents for potential treatment of Alzheimer's disease

2018 ◽  
Vol 79 ◽  
pp. 223-234 ◽  
Author(s):  
Leili Jalili-Baleh ◽  
Hamid Nadri ◽  
Hamid Forootanfar ◽  
Alireza Samzadeh-Kermani ◽  
Tuba Tüylü Küçükkılınç ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Lipoic Acid ◽  
Potential Treatment
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