Bioactive Pyrazolone Derived Thiazolidinone Scaffolds As a Safe Perspective to Human Health: Anti‐Alzheimer's, DFT, ADMET, and Molecular Docking Insight

Abstract In an approach to impede the activity of acetylcholinesterase and butyrylcholinesterase enzymes to treat Alzheimer's disease, hybrid pyrazolone derived thiazolidinone‐based chalcone scaffolds 1–14 were synthesized in the current research work. Structural validation of these compounds was accomplished by 1 HNMR, 13 CNMR, and HREI‐MS. Biological inhibitory potential of these compounds was assessed against AChE and BuChE in comparison to the standard drug, donepezil. These derivatives displayed excellent‐to‐moderate activity against these target enzymes. The minimum inhibition concentration for the novel derivatives against AChE was found ranging between 3.20 ± 0.10 to 20.10 ± 0.40 µM and against BuChE the range was found as 3.70 ± 0.50 to 21.10 ± 0.10 µM . Among the members of synthesized series, analog 8 emerged as the excellent inhibitor with striking efficacy against both enzymes. Computational analysis molecular docking was conducted to confirm the binding interactions of potent analogues with the target enzymes, AChE and BuChE. Electronic structure, stability, as well as reactivity toward targeted enzyme complexes were explored by DFT analysis. Moreover, drug likeness characteristics of active analogues were also predicted via ADMET analysis. All the in vitro and in silico results reveal that the lead compounds of the series have promising potential as therapeutic agents against Alzheimer's disease for future treatment.