Synthesis and Biological Evaluation of Benzoxazolone−Thiosemicarbazide, 1,2,4‐Triazole, 1,3,4‐Thiadiazole Derivatives as Cholinesterase Inhibitors.

In this study, a new series of benzoxazolone−thiosemicarbazide/1,2,4‐triazole/1,3,4‐thiadiazole hybrids were designed and synthesized. The structures of novel compounds were elucidated by spectral methods (IR, 1H‐NMR, 13C‐NMR, ESI‐MS) and elemental analyses. Acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibition activity of the compounds were investigated using in vitro Ellman method using donepezil and tacrin as the standards. Although none of compounds showed significant inhibitor activity on BuChE, compounds 2 c, 3 a, 4 a and 5 b displayed good inhibitory activities on AChE with IC50 values of 0.031, 0.049, 0.117 and 0.085 μg/mL, respectively. Molecular docking studies were carried out performed to the interactions with the active site of the enzyme (PDB:4EY7) and enzyme kinetics studies were performed for the most potent AChE inhibitor compound 2 c. [ABSTRACT FROM AUTHOR]