Exploiting butyrylcholinesterase inhibitors through a combined 3-D pharmacophore modeling, QSAR, molecular docking, and molecular dynamics investigation

Abstract

Alzheimer's disease (AD), a neurodegenerative condition associated with ageing, can occur.

“Click Chemistry”: An Emerging Tool for Developing a New Class of Structural Motifs against Various Neurodegenerative Disorders

“…The targeted BChE suppression improved learning and persistence in rats by raising ACh levels. Similar results were obtained in a mouse model of cholinergic deficiency, where in vivo BChE inhibition improved learning, memory, and cognitive performance . Tacrine, which was the first commercially available AChE/BChE inhibitor that had a noncompetitive, readily reversible inhibitory mechanism, was removed from the market in 2013 due to significant hepatotoxicity and is utilized solely as a reference today .…”

“…Similar results were obtained in a mouse model of cholinergic deficiency, where in vivo BChE inhibition improved learning, memory, and cognitive performance. 43 Tacrine, which was the first commercially available AChE/BChE inhibitor that had a noncompetitive, readily reversible inhibitory mechanism, was removed from the market in 2013 due to significant hepatotoxicity and is utilized solely as a reference today. 41 The BACE1 constitutes the buildup of amyloid proteins within the brain cells, which results in plaque formation.…”

Network Pharmacology Approach to Identify the Calotropis Phytoconstituents’ Potential Epileptic Targets and Evaluation of Molecular Docking, MD Simulation, and MM‐PBSA Performance

“…RMSF plots were generated to estimate the flexibility and mobility of individual amino acid residues during dynamic simulation (Figure S6). The high and low RMSF values distinguish the flexible and rigid regions of the amino acids, respectively [53] . The RMSF plot clearly shows that the average RMSF values of ergost‐5‐en‐3‐ol, stigmasterol, β‐sitosterol, and co‐crystallized ligands bound to PPAR‐γ and PTGS2 proteins were (0.113, 0.125, 0.111 and 0.115 nm) and (0.131, 0.114, 0.127 and 0.134 nm).…”

“…The high and low RMSF values distinguish the flexible and rigid regions of the amino acids, respectively. [53] The RMSF plot clearly shows that the average RMSF values of ergost-5-en-3-ol, stigmasterol, β-sitosterol, and co-crystallized ligands bound to PPAR-γ and PTGS2 proteins were (0.113, 0.125, 0.111 and 0.115 nm) and (0.131, 0.114, 0.127 and 0.134 nm). Notably, amino acids 243-245, 257-273 and 425-430 of PPAR-γ exhibited the highest fluctuation (Figure S6a).…”

Piperidine: A Versatile Heterocyclic Ring for Developing Monoamine Oxidase Inhibitors

“…Ammonia, aldehyde, and hydrogen peroxide are the three main intermediates produced through MAO-accelerated oxidative deamination. , MAO-A inhibitors are regarded as efficient therapeutic medicines for the treatment of neurological diseases, including anxiety and depression . MAO-B is one of the isozymes of MAO that is associated with neurodegeneration because its activity is markedly elevated in the brains of patients with AD . MAO inhibitors, which are involved in the oxidative deamination pathway, might diminish the buildup of oxidative stress mediators, such as hydrogen peroxide, aldehydes, and ammonia, possibly slowing the progression of AD .…”