Synthesis, In Vitro Biological Evaluation and In Silico Molecular Docking Studies of Indole Based Thiadiazole Derivatives as Dual Inhibitor of Acetylcholinesterase and Butyrylchloinesterase

Document Type

Article

Publication Date

11-1-2022

Abstract

The current study was conducted to obtain hybrid analogues of indole-based thiadiazole derivatives (1–16) in which a number of reaction steps were involved. To examine their biological activity in the presence of the reference drug Donepezil (0.21 ± 0.12 and 0.30 ± 0.32 M, respectively), the inhibitory potentials of AChE and BuChE were determined for these compounds. Different substituted derivatives showing a varied range of inhibitory profiles, when compared to the reference drug, analogue 8 was shown to have potent activity, with IC50 values for AchE 0.15 ± 0.050 M and BuChE 0.20 ± 0.10, respectively, while other substituted compounds displayed good to moderate potentials. Varied spectroscopic techniques including 1H, 13CNMR and HREI-MS were used to identify the basic skeleton of these compounds. Furthermore, all analogues have a known structure–activity relationship (SAR), and molecular docking investigations have verified the binding interactions of molecule to the active site of enzymes.

Publication Title

Molecules

DOI

10.3390/molecules27217368

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