Dataset Information

Potential Therapeutic Approaches to Alzheimer's Disease By Bioinformatics, Cheminformatics And Predicted Adme-Tox Tools.

ABSTRACT:

Background

Alzheimer's disease (AD) is considered a severe, irreversible and progressive neurodegenerative disorder. Currently, the pharmacological management of AD is based on a few clinically approved acethylcholinesterase (AChE) and N-methyl-D-aspartate (NMDA) receptor ligands, with unclear molecular mechanisms and severe side effects.

Methods

Here, we reviewed the most recent bioinformatics, cheminformatics (SAR, drug design, molecular docking, friendly databases, ADME-Tox) and experimental data on relevant structurebiological activity relationships and molecular mechanisms of some natural and synthetic compounds with possible anti-AD effects (inhibitors of AChE, NMDA receptors, beta-secretase, amyloid beta (A?), redox metals) or acting on multiple AD targets at once. We considered: (i) in silico supported by experimental studies regarding the pharmacological potential of natural compounds as resveratrol, natural alkaloids, flavonoids isolated from various plants and donepezil, galantamine, rivastagmine and memantine derivatives, (ii) the most important pharmacokinetic descriptors of natural compounds in comparison with donepezil, memantine and galantamine.

Results

In silico and experimental methods applied to synthetic compounds led to the identification of new AChE inhibitors, NMDA antagonists, multipotent hybrids targeting different AD processes and metal-organic compounds acting as A? inhibitors. Natural compounds appear as multipotent agents, acting on several AD pathways: cholinesterases, NMDA receptors, secretases or A?, but their efficiency in vivo and their correct dosage should be determined.

Conclusion

Bioinformatics, cheminformatics and ADME-Tox methods can be very helpful in the quest for an effective anti-AD treatment, allowing the identification of novel drugs, enhancing the druggability of molecular targets and providing a deeper understanding of AD pathological mechanisms.

SUBMITTER: Avram S

PROVIDER: S-EPMC7536829 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Potential Therapeutic Approaches to Alzheimer's Disease By Bioinformatics, Cheminformatics And Predicted Adme-Tox Tools.

Avram Speranta S Mernea Maria M Limban Carmen C Borcan Florin F Chifiriuc Carmen C

Current neuropharmacology 20200101 8

<h4>Background</h4>Alzheimer's disease (AD) is considered a severe, irreversible and progressive neurodegenerative disorder. Currently, the pharmacological management of AD is based on a few clinically approved acethylcholinesterase (AChE) and N-methyl-D-aspartate (NMDA) receptor ligands, with unclear molecular mechanisms and severe side effects.<h4>Methods</h4>Here, we reviewed the most recent bioinformatics, cheminformatics (SAR, drug design, molecular docking, friendly databases, ADME-Tox) an ...[more]

PMID: 31885353

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Dataset Information

Potential Therapeutic Approaches to Alzheimer's Disease By Bioinformatics, Cheminformatics And Predicted Adme-Tox Tools.

Background

Methods

Results

Conclusion

Publications

Potential Therapeutic Approaches to Alzheimer's Disease By Bioinformatics, Cheminformatics And Predicted Adme-Tox Tools.

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