scholarly journals Comparative Molecular Docking Analysis of Phytoconstituents against Alzheimer’s Disease Targets- An In-Silico Approach

2021 ◽  
Vol 12 (2) ◽  
pp. 1579-1589
Author(s):  
Geethanjali T ◽  
Logesh Kumar S ◽  
Keerthish Sujan B ◽  
Lakshmi Prabhaa M ◽  
Khousikan K ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Alzheimer Disease ◽  
Medicinal Plants ◽  
Panax Ginseng ◽  
In Silico ◽  
Docking Analysis ◽  
In Silico Docking

Alzheimer's disease (AD) is the most common form of dementia and one of the leading causes of death. The Aim and objective of the present study is to perform in-silico docking analysis of the major active constituents identified in three Indian medicinal plants namely Convolvulus pluricaulis, Coriandrum sativum and Panax ginseng for its effectiveness against the targets of Alzheimer Disease. In-silico docking analysis was performed by Molegro Virtual Docker (MVD-2010, 4.2.0) and Schrodinger Mestro (V 11.8). In addition, Drug likeness property, pharmacokinetics (ADME) and safety profile prediction studies were performed to identify the best drug candidates using Qikpro and Toxicity Estimation Software Tool (T.E.S.T). The target for Alzheimer Disease is Acetylcholinesterase and Butyrylcholinesterase. The X-ray crystal co-ordinates of AChE (PDB ID: 4bdt) and BChE (PDB ID: 6eqq) obtained from the Protein Data Bank. The phytoconstituents of three medicinal plants were retrieved from PubChem compound database in mol format. The standard drugs Donepezil, Rivastigmine, Galantamine, Memantine was obtained from the drug bank in .mol format for comparison. It was analysed from the parameters of docking that the phytoconstituents from Panax ginseng showed better anti-Alzheimer activity compared to that of the standard drugs. Based on the research findings, further studies can be performed in in-vitro & in-vivo animal models of Alzheimer’s disease to establish the efficacy of promising phytoconstituents.

In vitro and in vivo activities of imipenem combined with BLI-489 against class D β-lactamase-producing Acinetobacter baumannii

2020 ◽  
Author(s):  
Yung-Chih Wang ◽  
Shu-Wei Huang ◽  
Ming-Hsien Chiang ◽  
I-Ming Lee ◽  
Shu-Chen Kuo ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
In Silico ◽  
Active Sites ◽  
Synergistic Effects ◽  
Docking Analysis ◽  
In Silico Docking ◽  
Class D ◽  
Time Kill

Abstract Background According to our preliminary study, BLI-489 has the potential to inhibit the hydrolysing activity of OXA-51-like β-lactamase produced by carbapenem-resistant Acinetobacter baumannii (CRAb). Objectives In the present study, the in vitro and in vivo activities of imipenem combined with BLI-489 against CRAb producing carbapenem-hydrolysing class D β-lactamases (CHDLs), namely OXA-23, OXA-24, OXA-51 and OXA-58, were determined. Methods A chequerboard analysis of imipenem and BLI-489 was performed using 57 and 7 clinical CRAb isolates producing different CHDLs and MBLs, respectively. Four representative strains harbouring different CHDL genes were subjected to a time–kill assay to evaluate the synergistic effects. An in silico docking analysis was conducted to simulate the interactions between BLI-489 and the different families of CHDLs. The in vivo activities of this combination were assessed using a Caenorhabditis elegans survival assay and a mouse pneumonia model. Results Chequerboard analysis showed that imipenem and BLI-489 had a synergistic effect on 14.3, 92.9, 100, 16.7 and 100% of MBL-, OXA-23-, OXA-24-like-, OXA-51-like- and OXA-58-producing CRAb isolates, respectively. In the time–kill assay, imipenem and BLI-489 showed synergy against OXA-24-like-, OXA-51-like- and OXA-58-, but not OXA-23-producing CRAb isolates after 24 h. The in silico docking analysis showed that BLI-489 could bind to the active sites of OXA-24 and OXA-58 to confer strong inhibition activity. The combination of imipenem and BLI-489 exhibited synergistic effects for the rescue of CRAb-infected C. elegans and mice. Conclusions Imipenem combined with BLI-489 has synergistic effects against CHDL-producing CRAb isolates.

Thioflavin-based molecular probes for application in Alzheimer's disease: from in silico to in vitro models

Metallomics ◽  
2015 ◽  
Vol 7 (1) ◽  
pp. 83-92 ◽  
Author(s):  
C. Rodríguez-Rodríguez ◽  
M. A. Telpoukhovskaia ◽  
J. Alí-Torres ◽  
L. Rodríguez-Santiago ◽  
Y. Manso ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
In Silico ◽  
In Vitro Models ◽  
Molecular Probes ◽  
Drug Candidate ◽  
Chemical Tools

The proposed ThT-based drug candidate series is validated as chemical tools for further in vivo development.

P2-511: From in silico to in vitro to in vivo: - Novel approach in Alzheimer's disease drug discovery

2011 ◽  
Vol 7 ◽  
pp. S476-S476 ◽  
Author(s):  
Jun Wang ◽  
David Land ◽  
Jorge Galvez ◽  
Giulio Pasinetti
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Drug Discovery ◽  
In Silico ◽  
Novel Approach

scholarly journals Novel Multitarget Hydroxamic Acids with a Natural Origin CAP Group against Alzheimer’s Disease: Synthesis, Docking and Biological Evaluation

Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1893
Author(s):  
Margarita Neganova ◽  
Yulia Aleksandrova ◽  
Evgenii Suslov ◽  
Evgenii Mozhaitsev ◽  
Aldar Munkuev ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
In Silico ◽  
Hydroxamic Acid ◽  
Hydroxamic Acids ◽  
Biological Evaluation ◽  
Amide Bond ◽  
Morris Water Maze Test

Hydroxamic acids are one of the most promising and actively studied classes of chemical compounds in medicinal chemistry. In this study, we describe the directed synthesis and effects of HDAC6 inhibitors. Fragments of adamantane and natural terpenes camphane and fenchane, combined with linkers of various nature with an amide group, were used as the CAP groups. Accordingly, 11 original target compounds were developed, synthesized, and exposed to in vitro and in vivo biological evaluations, including in silico methods. In silico studies showed that all synthesized compounds were drug-like and could penetrate through the blood–brain barrier. According to the in vitro testing, hydroxamic acids 15 and 25, which effectively inhibited HDAC6 and exhibited anti-aggregation properties against β-amyloid peptides, were chosen as the most promising substances to study their neuroprotective activities in vivo. All in vivo studies were performed using 5xFAD transgenic mice simulating Alzheimer’s disease. In these animals, the Novel Object Recognition and Morris Water Maze Test showed that the formation of hippocampus-dependent long-term episodic and spatial memory was deteriorated. Hydroxamic acid 15 restored normal memory functions to the level observed in control wild-type animals. Notably, this effect was precisely associated with the ability to restore lost cognitive functions, but not with the effect on motor and exploratory activities or on the level of anxiety in animals. Conclusively, hydroxamic acid 15 containing an adamantane fragment linked by an amide bond to a hydrocarbon linker is a possible potential multitarget agent against Alzheimer’s disease.

Natural Anti-inflammatory compounds as Drug candidates in Alzheimer’s disease

2020 ◽  
Vol 27 ◽  
Author(s):  
Reyaz Hassan Mir ◽  
Abdul Jalil Shah ◽  
Roohi Mohi-ud-din ◽  
Faheem Hyder Potoo ◽  
Mohd. Akbar Dar ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Natural Products ◽  
Protective Action ◽  
New Drugs ◽  
Huperzine A ◽  
Brain Disorder ◽  
Anti Inflammatory

: Alzheimer's disease (AD) is a chronic neurodegenerative brain disorder characterized by memory impairment, dementia, oxidative stress in elderly people. Currently, only a few drugs are available in the market with various adverse effects. So to develop new drugs with protective action against the disease, research is turning to the identification of plant products as a remedy. Natural compounds with anti-inflammatory activity could be good candidates for developing effective therapeutic strategies. Phytochemicals including Curcumin, Resveratrol, Quercetin, Huperzine-A, Rosmarinic acid, genistein, obovatol, and Oxyresvertarol were reported molecules for the treatment of AD. Several alkaloids such as galantamine, oridonin, glaucocalyxin B, tetrandrine, berberine, anatabine have been shown anti-inflammatory effects in AD models in vitro as well as in-vivo. In conclusion, natural products from plants represent interesting candidates for the treatment of AD. This review highlights the potential of specific compounds from natural products along with their synthetic derivatives to counteract AD in the CNS.

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.

Electromagnetic field in Alzheimer’s disease: a literature review of recent preclinical and clinical studies

2020 ◽  
Vol 17 ◽  
Author(s):  
Reem Habib Mohamad Ali Ahmad ◽  
Marc Fakhoury ◽  
Nada Lawand
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
In Vivo Studies ◽  
Key Factors ◽  
Potential Benefits ◽  
Preclinical And Clinical Studies ◽  
The Brain

: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the progressive loss of neurons leading to cognitive and memory decay. The main signs of AD include the irregular extracellular accumulation of amyloidbeta (Aβ) protein in the brain and the hyper-phosphorylation of tau protein inside neurons. Changes in Aβ expression or aggregation are considered key factors in the pathophysiology of sporadic and early-onset AD and correlate with the cognitive decline seen in patients with AD. Despite decades of research, current approaches in the treatment of AD are only symptomatic in nature and are not effective in slowing or reversing the course of the disease. Encouragingly, recent evidence revealed that exposure to electromagnetic fields (EMF) can delay the development of AD and improve memory. This review paper discusses findings from in vitro and in vivo studies that investigate the link between EMF and AD at the cellular and behavioural level, and highlights the potential benefits of EMF as an innovative approach for the treatment of AD.

Targeting PPARalpha in Alzheimer's Disease

2018 ◽  
Vol 15 (4) ◽  
pp. 345-354 ◽  
Author(s):  
Barbara D'Orio ◽  
Anna Fracassi ◽  
Maria Paola Cerù ◽  
Sandra Moreno
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Mechanisms ◽  
Redox Homeostasis ◽  
Antioxidant Response ◽  
Peroxisome Proliferator ◽  
Prevailing Paradigm

Background: The molecular mechanisms underlying Alzheimer's disease (AD) are yet to be fully elucidated. The so-called “amyloid cascade hypothesis” has long been the prevailing paradigm for causation of disease, and is today being revisited in relation to other pathogenic pathways, such as oxidative stress, neuroinflammation and energy dysmetabolism. The peroxisome proliferator-activated receptors (PPARs) are expressed in the central nervous system (CNS) and regulate many physiological processes, such as energy metabolism, neurotransmission, redox homeostasis, autophagy and cell cycle. Among the three isotypes (α, β/δ, γ), PPARγ role is the most extensively studied, while information on α and β/δ are still scanty. However, recent in vitro and in vivo evidence point to PPARα as a promising therapeutic target in AD. Conclusion: This review provides an update on this topic, focussing on the effects of natural or synthetic agonists in modulating pathogenetic mechanisms at AD onset and during its progression. Ligandactivated PPARα inihibits amyloidogenic pathway, Tau hyperphosphorylation and neuroinflammation. Concomitantly, the receptor elicits an enzymatic antioxidant response to oxidative stress, ameliorates glucose and lipid dysmetabolism, and stimulates autophagy.

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