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.