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

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.

Discovery of Thiadiazoles as Human Dihydroorotate Dehydrogenase (hDHODH) Inhibitors by Combined Structure‐Based Modelling Methods

“…[1] Our approach included construction of structure-based pharmacophore model for screening of the zinc database, molecular docking, Mechanics Generation Born Surface Area (MM-GBSA) calculations, molecular dynamics (MD) studies, and physicochemical and ADMET properties prediction studies to design novel thiadiazole derivatives as hDHODH inhibitors. [49][50][51][52][53]…”

Effect of Ru on Deformation Mechanism and Microstructure Evolution of Single-Crystal Superalloys under Medium-Temperature and High-Stress Creep

“…However, the addition of Re makes the microstructural homogenization during solution heat treatment more difficult due to its low diffusivity and severe micro-segregation. Additionally, at high temperatures and long-term exposure, there is the formation of topologically close-packed (TCP) phases in Re containing superalloys, which becomes detrimental to the creep properties of the alloy by depletion of important strengthening elements from the matrix, the cracks initiation induced by the stress concentration [ 11 , 12 , 13 ]. This deleterious effect of Re necessitated the introduction of Ru in Ni-based single-crystal superalloys.…”

Nitrogen Doped Porous Biochar/β-CD-MOFs Heterostructures: Bi-Functional Material for Highly Sensitive Electrochemical Detection and Removal of Acetaminophen

“…Up until now, adsorption has been considered a reliable technology for removing pollution from groundwater because of the advantages of excellent removal effect and ease of operation [ 5 ]. At the same time, electrochemical detection technology is widely used in various fields due to its high accuracy, rapid detection, easy miniaturization and real-time monitoring [ 6 , 7 , 8 ]. Considering that the performance of the electrochemical sensor is primarily decided by two aspects, one being the enrichment ability of electrode modification materials toward the detection substances and the other being their catalytic performance.…”