Benzene-1,3-diol derivatives as the inhibitors of butyrylcholinesterase: An emergent target of Alzheimer’s disease

Abstract

Molecular docking is a powerful and significant approach for the identification of lead molecules on the basis of virtual screening. With this a large number of compounds can be tested and based on the scoring function and ranking, the conclusion can be made that how the selected compounds can inhibit the targeted protein/receptor. By keeping in view, the importance of selective inhibitors of cholinesterase in the treatment of Alzheimer disease, here we are focused on the determination of the mechanism of binding interactions of few benzene-1,3-diol derivatives within the active site of both acetyl-cholinesterase (AChE) and butyrylcholinesterase (BChE). All the selective ligands were found to have a greater binding affinity with the BChE as compared to that of AChE, by an average value of ~?28.4 and ~?12.5 kJ/mol, respectively. The results suggested that the identified inhibitors can be used as the lead candidates for the development of novel inhibitors of the targeted enzymes against specific diseases, thus opening the possibility of new therapeutic strategies.

4-Phthalimidobenzenesulfonamide Derivatives as Acetylcholinesterase and Butyrylcholinesterase Inhibitors: DFTs, 3D-QSAR, ADMET, and Molecular Dynamics Simulation

“…Molecular docking analysis on the synthesized 4-phthalimidobenzenesulfonamide analogs has already been done to predict the inhibitory mechanism against AChE and BChE, respectively [35][36][37]. The crystal structures of targeted protein targets, i.e., for AChE: 4BDT (PDB ID) and for BChE: 4BDS (PDB ID) were accessed from RCSB protein data bank [38], respectively.…”

In silico prediction of the inhibition of new molecules on SARS-CoV-2 3CL protease by using QSAR: PSOSVR approach

“…Moreover, 3CLpro has available biological evaluation experiments and relies on structural and genomic studies, making necessary data available (Tahir ul Qamar et al 2020 ). It interferes in the replication process (Yan and Gao 2021 ), where it is responsible for the cleavage of 11 non-structural proteins (nsp1 to nsp11) (De et al 2020 ) essential for viral replication and transcriptase (Dongliang et al 2022 ). In light of this evidence, 3CLpro is considered a valuable target in fighting against SARS-CoV-2.…”