In vitro and kinetic studies of thiazolidine-۲, ۴-dione derivative as potential butyrylcholinesterase inhibitor as a target in AD therapy

Alzheimer's disease (AD) is a chronic neurological disorder characterized by memory impairment, cognitive dysfunction, behavioral disturbances, and deficits in activities of daily living. Butyrylcholinesterase (BuChE: EC ۳.۱.۱.۸) is a glycoprotein found in central and peripheral nervous systems in most tissues. Two histopathological hallmarks of AD are neurofibrillary tangles, amyloid plaque and intense BuChE activity. Inhibition of this enzyme can be a main in the control of AD. In this study, the thiazolidine-۲, ۴-dione(TZD) derivative was selected to assay the inhibitory potential against the BuChE. This study aimed to determine the lowest concentration of TZD derivative to inhibit the BuChE enzyme. A kinetic analysis was carried out to study the inhibitory mechanism of the TZD derivative. Inhibitory assays were carried out with the synthesized compound on BuChE using Ellman's method. The optimal concentration was achieved by TZD derivative as an inhibitor and Butyrylthiocholin iodide (BTCI) as a BuChE substrate. Km and Vmas were determined using the Lineweaver-Burk plot and defined the type of enzyme inhibition by the TZD derivative. TZD derivative was an active compound against BuChE and showed noticeable inhibitory activity, above ۳۵% inhibition, against BuChE. According to the results of this investigation, the TZD derivative showed good inhibitory potential on BuChE

کلیدواژه ها:

Butyrylcholinesterase ، Alzheimer's disease ، thiazolidine-۲ ، ۴-dione ، Ellman's method