Background:
Alzheimer’s disease (AD), an irreversible complex neurodegenerative disorder, is most common
type of dementia, with progressive loss of cholinergic neurons. Based on the multi- factorial etiology of Alzheimer’s disease, novel ligands strategy appears as up-coming approach for the development of newer molecules against AD. This study
is envisaged to investigate anti-Alzheimer’s potential of 10 synthesized compounds. The screening of compounds (1-10)
was carried out using in silico techniques.
Methods:
For in silico screening of physicochemical properties of compounds molinspiration property engine v.2018.03,
Swiss ADME online web-server and pkCSM ADME were used. For pharmacodynamic prediction PASS software while
toxicity profile of compounds were analyzed through ProTox-II online software. Simultaneously, molecular docking analysis was performed on mouse AChE enzyme (PDB ID:2JGE, obtained from RSCB PDB) using Auto Dock Tools 1.5.6.
Results:
Based on in silico studies, compound 9 and 10 have been found to have better drug likeness, LD50 value, and better anti-Alzheimer’s, nootropic activities. However, these compounds had poor blood brain barrier (BBB) permeability.
Compound 4 and 9 were predicted with better docking score for AChE enzyme.
Conclusion:
The outcome of in silico studies have suggested, out of various substitutions at different positions of pyridoxine-carbamate, compound 9 have shown promising drug likeness, with better safety and efficacy profile for anti-Alzheimer’s
activity. However, BBB permeability appears as one the major limitation of all these compounds. Further studies are required to confirm its biological activities.
Selective lesions of the cholinergic neurons within the posterior pedunculopontine do not alter operant learning or nicotine sensitization
