Use of ligand-based pharmacophore modeling and docking approach to find novel acetylcholinesterase inhibitors for treating Alzheimer's

Dhanjal, Jaspreet Kaur; Sharma, Sudhanshu; Grover, Abhinav; Das, Asmita

doi:10.1016/j.biopha.2015.02.010

Cited by 36 publications

(20 citation statements)

References 27 publications

(24 reference statements)

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“…The pharmacophore-model-based screening of databases has been considered as an important tool for computer-aided drug discovery techniques and provides information about geometric and electronic features that are involved in interaction with receptors [ 21 ]. In this part, the chemical database comprised 1,033,419 molecules with lowest energy in 3D format and was generated by applying various filters.…”

Section: Resultsmentioning

confidence: 99%

Identification of Novel Src Inhibitors: Pharmacophore-Based Virtual Screening, Molecular Docking and Molecular Dynamics Simulations

Zhang

et al. 2020

Molecules

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Src plays a crucial role in many signaling pathways and contributes to a variety of cancers. Therefore, Src has long been considered an attractive drug target in oncology. However, the development of Src inhibitors with selectivity and novelty has been challenging. In the present study, pharmacophore-based virtual screening and molecular docking were carried out to identify potential Src inhibitors. A total of 891 molecules were obtained after pharmacophore-based virtual screening, and 10 molecules with high docking scores and strong interactions were selected as potential active molecules for further study. Absorption, distribution, metabolism, elimination and toxicity (ADMET) property evaluation was used to ascertain the drug-like properties of the obtained molecules. The proposed inhibitor–protein complexes were further subjected to molecular dynamics (MD) simulations involving root-mean-square deviation and root-mean-square fluctuation to explore the binding mode stability inside active pockets. Finally, two molecules (ZINC3214460 and ZINC1380384) were obtained as potential lead compounds against Src kinase. All these analyses provide a reference for the further development of novel Src inhibitors.

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Section: Resultsmentioning

confidence: 99%

Identification of Novel Src Inhibitors: Pharmacophore-Based Virtual Screening, Molecular Docking and Molecular Dynamics Simulations

Zhang

et al. 2020

Molecules

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“…ACh, released into the synapse from one neuron, binds to its receptor located on the postsynaptic membrane to transmit the signal to the next neuron. It is well known that a serine protease called acetylcholinesterase (AChE) catalyzes the degradation of the neurotransmitter ACh, leading to the termination of cholinergic neurotransmission . The activity of this enzyme increases in AD patients, making it a promising target to be inhibited for symptomatic treatment of the disease …”

Section: Introductionmentioning

confidence: 99%

“…It is well known that a serine protease called acetylcholinesterase (AChE) catalyzes the degradation of the neurotransmitter ACh, leading to the termination of cholinergic neurotransmission. [5] The activity of this enzyme increases in AD patients, making it a promising target to be inhibited for symptomatic treatment of the disease. [6] Until recently, four representative anti-AChE agents, tacrine, rivastigmine, donepezil and galantamine, have been approved by the Food and Drug Administration to treat the symptoms caused by cholinergic dysfunction in AD.…”

Section: Introductionmentioning

confidence: 99%

Identification of New Potent Acetylcholinesterase Inhibitors Using Virtual Screening and in vitro Approaches

Mokrani

Bensegueni

Chaput

et al. 2019

Molecular Informatics

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Acetylcholinesterase (AChE) is currently the most favorable target for the symptomatic treatment and reduction of Alzheimer's disease (AD). In order to identify new potent inhibitors of this enzyme, we describe herein a new structure‐based virtual screening (SBVS) using the Institut Curie‐CNRS chemical library (ICCL), which contained at the screening date 14307 compounds. The strategy undertaken in this work consisted of the use of several docking programs in SBVS calculations followed by the application of a consensus method (vSDC) and a scrupulous visual analysis. It allowed us to obtain a high degree of success, with a yield of almost 86 %, since 12 hits were identified among only 14 molecules tested in vitro. Still more remarkably, 6 of these hits were more active than galantamine, the reference inhibitor. These hits were predicted to have good ADMET properties. The two most promising compounds can serve as leads for AD treatment.

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“…17 Earlier researchers attempted to develop pharmacophore models and utilized them for virtual screening of database molecules to nd new AChE inhibitors. [18][19][20][21][22][23] Present work combines both ligand-based (3D-QSAR) and energy optimized structure-based pharmacophore (epharmacophore) approaches for virtual screening of free 'ZINC15' database molecules. The hits, as AChE inhibitors, were recognized by utilizing HTVS and molecular docking studies of pharmacophore matched compounds aer removal of panassay interference compounds (PAINS).…”

Section: Introductionmentioning

confidence: 99%

Multiple 3D-QSAR modeling, e-pharmacophore, molecular docking, and in vitro study to explore novel AChE inhibitors

2018

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Use of ligand-based pharmacophore modeling and docking approach to find novel acetylcholinesterase inhibitors for treating Alzheimer's

Cited by 36 publications

References 27 publications

Identification of Novel Src Inhibitors: Pharmacophore-Based Virtual Screening, Molecular Docking and Molecular Dynamics Simulations

Identification of Novel Src Inhibitors: Pharmacophore-Based Virtual Screening, Molecular Docking and Molecular Dynamics Simulations

Identification of New Potent Acetylcholinesterase Inhibitors Using Virtual Screening and in vitro Approaches

Multiple 3D-QSAR modeling, e-pharmacophore, molecular docking, and in vitro study to explore novel AChE inhibitors

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