Synthesis, characterization, DFT, AMDET and molecular docking reveals the binding mechanism of hydroxyl containing bis-Schiff base derivatives: An approach toward Alzheimer disease

One of the major neurodegenerative disorders, Alzheimer’s disease (AD) was targeted in the current study synthesizing bis-Schiff bases derivatives. All the synthesized scaffolds were found to have a range of IC50 values (2.50 ± 0.10 µM to 19.20 ± 0.10 µM) for AChE and (3.60 ± 0.10 µM to 19.90 ± 0.20 µM) for BuChE enzyme in comparison to reference drug donepezil (10.10 ± 0.20 µM to 11.50 ± 0.20 µM). Among the members of novel series, analogue 9 exhibited surpassing potential against both enzymes. Additionally, anti-fungal and anti-bacterial potential were also determined, where analog 9 showed higher anti-fungal inhibition (46.5 %) and analog 8 displayed strong inhibition potential (35.5 %) as anti-bacterial. Furthermore, in silico molecular docking approach was employed to explore the linkage between active site of proteins and active ligands. ADMET analysis conducted in this study predicted the drug nature of the lead compounds. The reactivity of the potent compounds for the attack of electrophile and nucleophile was elucidated via DFT. Moreover, the basic structural skeleton of the synthesized derivatives was characterized through modern methods of structure elucidation such as HREI-MS, 1H NMR and 13C NMR.