scholarly journals Structure–activity relationship, in vitro and in vivo evaluation of novel dienyl sulphonyl fluorides as selective BuChE inhibitors for the treatment of Alzheimer's disease

2021 ◽  
Vol 36 (1) ◽  
pp. 1860-1873
Author(s):  
Chengyao Wu ◽  
Guijuan Zhang ◽  
Zai-Wei Zhang ◽  
Xia Jiang ◽  
Ziwen Zhang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
In Vivo Evaluation ◽  
Structure Activity

Xanthone: Potential Acetylcholinesterase Inhibitor for Alzheimer's Disease Treatment

2021 ◽  
Vol 21 ◽  
Author(s):  
Vincentsia Vienna Vanessa ◽  
Siau Hui Mah
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Acetylcholinesterase Inhibitor ◽  
Structure Activity Relationship ◽  
Acetylcholinesterase Inhibition ◽  
Activity Relationship ◽  
Structure Activity ◽  
Hydrophobic Moiety

: Alzheimer's disease is a neurodegenerative disorder that results in progressive and irreversible central nervous system impairment, which has become one of the severe issues recently. The most successful approach of Alzheimer’s treatment is the administration of cholinesterase inhibitors to prevent the hydrolysis of acetylcholine and subsequently improve the cholinergic postsynaptic transmission. This review highlights a class of heterocycle, namely xanthone and its remarkable acetylcholinesterase inhibitory activities. Naturally occurring xanthones, including oxygenated, prenylated, pyrano and glycosylated xanthones exhibited promising inhibition effects towards acetylcholinesterase. Interestingly, synthetic xanthone derivatives with complex substituents such as alkyl, pyrrolidine, piperidine and morpholine have shown greater acetylcholinesterase inhibition activities. Structure-activity relationship of xanthones revealed that the type and position of substituent(s) attached to the xanthone moiety influenced their acetylcholinesterase inhibition activities where hydrophobic moiety will lead to an improved activity by contributing the π-π interactions, as well as the hydroxy substituent(s) by forming hydrogen-bond interactions. Thus, further studies including quantitative structure-activity relationship, in vivo and clinical validation studies are crucial for the development of xanthones into novel anti-Alzheimer's disease drugs.

Synthesis of new generation triazolyl- and isoxazolyl-containing 6-nitro-2,3-dihydroimidazooxazoles as anti-TB agents: in vitro, structure–activity relationship, pharmacokinetics and in vivo evaluation

2015 ◽  
Vol 13 (12) ◽  
pp. 3610-3624 ◽  
Author(s):  
Gurunadham Munagala ◽  
Kushalava Reddy Yempalla ◽  
Samsher Singh ◽  
Sumit Sharma ◽  
Nitin Pal Kalia ◽  
...  
Keyword(s):  
Structure Activity Relationship ◽  
Activity Relationship ◽  
In Vivo Evaluation ◽  
Structure Activity ◽  
New Generation

Promising nitroimidazoloxazole scaffold gives another novel triazolyl-containing 6-nitro-2,3-dihydroimidazooxazole as anti-TB lead.

In vivo Evaluation and Alzheimer’s Disease Treatment Outcome of siRNA Loaded Dual Targeting Drug Delivery System

2019 ◽  
Vol 20 (1) ◽  
pp. 56-62 ◽  
Author(s):  
Chi Zhang ◽  
Zhichun Gu ◽  
Long Shen ◽  
Xianyan Liu ◽  
Houwen Lin
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Treatment Outcome ◽  
Neuroprotective Effect ◽  
Sirna Delivery ◽  
Repeated Administration ◽  
Spatial Learning And Memory ◽  
In Vivo Evaluation

Background: To deliver drugs to treat Alzheimer’s Disease (AD), nanoparticles should firstly penetrate through blood brain barrier, and then target neurons. Methods: Recently, we developed an Apo A-I and NL4 dual modified nanoparticle (ANNP) to deliver beta-amyloid converting enzyme 1 (BACE1) siRNA. Although promising in vitro results were obtained, the in vivo performance was not clear. Therefore, in this study, we further evaluated the in vivo neuroprotective effect and toxicity of the ANNP/siRNA. The ANNP/siRNA was 80.6 nm with good stability when incubated with serum. In vivo, the treatment with ANNP/siRNA significantly improves the spatial learning and memory of APP/PS1 double transgenic mice, as determined by mean escape latency, times of crossing the platform area during the 60 s swimming and the percentage of the distance in the target quadrant. Results and Conclusion: After the treatment, BACE1 RNA level of ANNP/siRNA group was greatly reduced, which contributed a good AD treatment outcome. Finally, after repeated administration, the ANNP/siRNA did not lead to significant change as observed by HE staining of main organs, suggesting the good biocompatibility of ANNP/siRNA. These results demonstrated that the ANNP was a good candidate for AD targeting siRNA delivery.

Understanding the quantitative structure–activity relationship of acetylcholinesterase inhibitors for the treatment of Alzheimer's disease

2015 ◽  
Vol 14 (06) ◽  
pp. 1550040 ◽  
Author(s):  
Anuradha Sharma ◽  
Poonam Piplani
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Quantitative Structure Activity Relationship ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Structural Basis ◽  
Quantitative Structure ◽  
Structure Activity ◽  
Qsar Models ◽  
Relationship Of

Alzheimer's disease (AD) is the most common cause of dementia in old aged people and clinically used drugs for treatment are associated with side effects. Thus, there is a current demand for the discovery and development of new potential molecules. However, the recent advances in drug therapy have challenged the predominance of the disease. In this manuscript, an attempt has been made to develop the 2D and 3D quantitative structure–activity relationship (QSAR) models for a series of rutaecarpine, quinazolines and 7,8-dehydrorutaecarpine derivatives to obtain insights to Acetylcholinesterase (AChE) inhibition. Five different QSAR models have been generated and validated using a set of 52 compounds comprising of varying scaffolds with IC50 values ranging from 11,000 nM to 0.6 nM. These AChE-specific prediction models (M1–M5) adequately reflect the structure–activity relationship of the existing AChE inhibitors. Out of all developed models, QSAR model generated using ADME properties has been found to be the best with satisfactory statistical significance (regression (r2) of 0.9309 and regression adjusted coefficient of variation [Formula: see text] of 0.9194). The QSAR models highlight the importance of aromatic moiety as their presence in the structure influence the biological activity. Additional insights on the compounds show that acyclic amines attached to side chain have lower activity than cyclic amines. The QSAR models pinpointing structural basis for the AChEIs suggest new guidelines for the design of novel molecules.

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