Tutus_2024_Drug.Dev.Res_85_e22214

In this study, the synthesis of N-(5,6-methylenedioxybenzothiazole-2-yl)-2-[(substituted)thio/piperazine]acetamide/propanamide derivatives (3a-3k) and to investigate their acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and beta-secretase 1 (BACE-1) inhibition activity were aimed. Mass, (1)H NMR, and (13)C NMR spectra were utilized to determine the structure of the synthesized compounds. Compounds 3b, 3c, 3f, and 3j showed AChE inhibitory activity which compound 3c (IC(50) = 0.030 +/- 0.001 microM) showed AChE inhibitory activity as high as the reference drug donepezil (IC(50) = 0.0201 +/- 0.0010 microM). Conversely, none of the compounds showed BChE activity. Compounds 3c and 3j showed the highest BACE-1 inhibitory activity and IC(50) value was found as 0.119 +/- 0.004 microM for compound 3j whereas IC(50) value was 0.110 +/- 0.005 microM for donepezil, which is one of the reference substance. Molecular docking studies have been carried out using the data retrieved from the server of the Protein Data Bank (PDBID: 4EY7 and 2ZJM). Using in silico approach behavior active compounds (3c and 3j) and their binding modes clarified.