Virtual Screening and Biological Evaluation of Piperazine Derivatives as Human Acetylcholinesterase Inhibitors

Varadaraju, Kavitha Raj; Kumar, Jajur Ramanna; Mallesha, L.; Archana, Muruli; Mohana, K. N.; Mukunda, Chethan Kumar; Umesha, S.

doi:10.1155/2013/653962

Cited by 18 publications

(10 citation statements)

References 47 publications

(54 reference statements)

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“…For instance, carbamates are the main player responsible for the bioactivity of rivastigmine, which is an acetylcholinesterase inhibitor used for the treatment of Alzheimer's and Parkinson's disease (Youdim et al, 2014). Piperazines have also displayed a range of biological activities including neuroprotective effects (Varadaraju et al, 2013;Modi et al, 2014;Wang et al, 2016). The quinolinol moiety is a strong radical scavenger present in Tacrine, the first drug approved for the treatment of AD (Ferná Ndez-Bachiller et al, 2010).…”

Section: Fungal Benzofuran Natural Products Are a Prolific Source Of mentioning

confidence: 99%

Exploring the Multi–Target Neuroprotective Chemical Space of Benzofuran Scaffolds: A New Strategy in Drug Development for Alzheimer’s Disease

et al. 2020

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Section: Fungal Benzofuran Natural Products Are a Prolific Source Of mentioning

confidence: 99%

Exploring the Multi–Target Neuroprotective Chemical Space of Benzofuran Scaffolds: A New Strategy in Drug Development for Alzheimer’s Disease

et al. 2020

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“…We choose the AChE holo-protein complexed with the anti-alzheimer drug E20 marketed as Ariceptand (PDB code 1EVE) ( 27 ). This protein consisting of 534 residues, was used for recent computational investigations ( 28 , 29 ). AChe, denoted as 1eve for the rest of this study, was not included in the training set used to build PockDrug model.…”

Section: Introductionmentioning

confidence: 99%

PockDrug-Server: a new web server for predicting pocket druggability on holo and apo proteins

et al. 2015

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Predicting protein pocket's ability to bind drug-like molecules with high affinity, i.e. druggability, is of major interest in the target identification phase of drug discovery. Therefore, pocket druggability investigations represent a key step of compound clinical progression projects. Currently computational druggability prediction models are attached to one unique pocket estimation method despite pocket estimation uncertainties. In this paper, we propose ‘PockDrug-Server’ to predict pocket druggability, efficient on both (i) estimated pockets guided by the ligand proximity (extracted by proximity to a ligand from a holo protein structure) and (ii) estimated pockets based solely on protein structure information (based on amino atoms that form the surface of potential binding cavities). PockDrug-Server provides consistent druggability results using different pocket estimation methods. It is robust with respect to pocket boundary and estimation uncertainties, thus efficient using apo pockets that are challenging to estimate. It clearly distinguishes druggable from less druggable pockets using different estimation methods and outperformed recent druggability models for apo pockets. It can be carried out from one or a set of apo/holo proteins using different pocket estimation methods proposed by our web server or from any pocket previously estimated by the user. PockDrug-Server is publicly available at: http://pockdrug.rpbs.univ-paris-diderot.fr.

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“…40 Glutamate-mediated synaptic transmission is vital for the normal functioning of the nervous system with glutamate being the most important excitatory neurotransmitter in the brain. 41 Hyperactivation of the NMDA receptor with glutamate leads to the production of free radicals and other enzymes that contribute to the death of neuronal cells.…”

Section: N-methyl-d-aspartate Receptormentioning

confidence: 99%

Current and novel therapeutic molecules and targets in Alzheimer's disease

Kumar

Nisha

Silakari

et al. 2016

Journal of the Formosan Medical Association

126

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Alzheimer's disease (AD) is a neurodegenerative disorder in which the death of brain cells causes memory loss and cognitive decline, i.e., dementia. The disease starts with mild symptoms and gradually becomes severe. AD is one of the leading causes of mortality worldwide. Several different hallmarks of the disease have been reported such as deposits of β-amyloid around neurons, hyperphosphorylated tau protein, oxidative stress, dyshomeostasis of bio-metals, low levels of acetylcholine, etc. AD is not simple to diagnose since there is no single diagnostic test for it. Pharmacotherapy for AD currently provides only symptomatic relief and mostly targets cognitive revival. Computational biology approaches have proved to be reliable tools for the selection of novel targets and therapeutic ligands. Molecular docking is a key tool in computer-assisted drug design and development. Docking has been utilized to perform virtual screening on large libraries of compounds, and propose structural hypotheses of how the ligands bind with the target with lead optimization. Another potential application of docking is optimization stages of the drug-discovery cycle. This review summarizes the known drug targets of AD, in vivo active agents against AD, state-of-the-art docking studies done in AD, and future prospects of the docking with particular emphasis on AD.

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Virtual Screening and Biological Evaluation of Piperazine Derivatives as Human Acetylcholinesterase Inhibitors

Cited by 18 publications

References 47 publications

Exploring the Multi–Target Neuroprotective Chemical Space of Benzofuran Scaffolds: A New Strategy in Drug Development for Alzheimer’s Disease

Exploring the Multi–Target Neuroprotective Chemical Space of Benzofuran Scaffolds: A New Strategy in Drug Development for Alzheimer’s Disease

PockDrug-Server: a new web server for predicting pocket druggability on holo and apo proteins

Current and novel therapeutic molecules and targets in Alzheimer's disease

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