Speranta Avram, Maria Mernea*, Carmen Limban, Florin Borcan and Carmen Chifiriuc Pages 1 - 24 ( 24 )
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 structure-biological 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 (Aβ), 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 Aβ inhibitors. Natural compounds appear as multipotent agents, acting on several AD pathways: cholinesterases, NMDA receptors, secretases or Aβ, but their efficiency in vivo and their correct dosage is to 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.
Alzheimer’s disease, bioinformatics, cheminformatics, synthetic and natural compounds, QSAR, docking
Department of Anatomy, Animal Physiology and Biophysics, Faculty of Biology, University of Bucharest, Bucharest, Department of Anatomy, Animal Physiology and Biophysics, Faculty of Biology, University of Bucharest, Bucharest, Department of Pharmaceutical Chemistry, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Department of Analytical Chemistry, Faculty of Pharmacy, “Victor Babes” University of Medicine and Pharmacy, Timisoara, Department of Botanic-Microbiology, Faculty of Biology, University of Bucharest, Research Institute of University of Bucharest- ICUB, Bucharest