Identification of Potent Inhibitors of Alzheimer's Disease Based on Benzodioxin‐Thiosemicarbazide Analogues and Molecular Docking Study

Abstract Alzheimer's is a long‐term neurodegenerative illness that causes brain cells to deteriorate and has an especially negative impact on a person's capacity for independent functioning. Despite ongoing research, there is no effective cure for the disease, although early intervention can reduce its long‐lasting effects. In search for the more effective drugs for the treatment of Alzheimer's disease we have synthesized a new series of benzodioxine‐based thiosemicabazides derivatives ( 1 – 16 ) and screened them for AChE and BuChE inhibition potential. Most of the analogues of the series showed good inhibition potential, having IC 50 values ranging from 0.10 ± 0.01 to 6.10 ± 0.30 µM for AChE and 0.10 ± 0.01 to 5.20 ± 0.30 µM for BuChE under the positive control of the standard drug donepezil, having a value of 0.016 ± 0.01 µM for AChE and 0.30 ± 0.010 µM for BuChE. Analogues 1, 3, 7, 9 , and 13 demonstrated potent inhibition in this investigation. Using spectroscopic methods such as 1 H NMR, 13 C NMR, and HR‐EI‐MS, all the synthesized analogues were characterized. Structure activity relationship has been established for all compounds. Molecular docking study was carried out to confirm the binding interaction between enzyme active site and compounds.