BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol.26, no.22, pp.5387-5394, 2016 (SCI-Expanded)
In the current study, 14 new benzothiazole-piperazine compounds were designed to meet the structural requirements of acetylcholine esterase (AChE) inhibitors. The target compounds were synthesised in three steps. Structures of the newly synthesised compounds (7-20) were confirmed using IR, H-1 NMR, C-13 NMR, and HRMS methods. The inhibitory potential of the compounds on AChE (E.C.220.127.116.11, from electric eel) was then investigated. Among the compounds, 19 and 20 showed very good activity on AChE enzyme. Kinetics studies were performed to observe the effects of the most active compounds on the substrate-enzyme relationship. Cytotoxicity studies, genotoxicity studies, and theoretical calculation of pharmacokinetics properties were also carried out. The compounds 19 and 20 were found to be nontoxic in both of the toxicity assays. A good pharmacokinetics profile was predicted for the synthesised compounds. Molecular docking studies were performed for the most active compounds, 19 and 20, and interaction modes with enzyme active sites were determined. Docking studies indicated a strong interaction between the active sites of AChE enzyme and the analysed compounds. (C) 2016 Elsevier Ltd. All rights reserved.