In Silico Investigation of Suillin Derived from Suillus luteus Mushroom (Agaricomycetes) Targeting Acetylcholinesterase: Docking and Virtual Screening Study.

This study integrates bioinformatics and computer-aided drug discovery to assess suillin's therapeutic potential, particularly its interaction with acetylcholinesterase (AChE). Alzheimer's disease presents profound challenges, necessitating effective treatments to mitigate cognitive decline and improve patients' quality of life. Although current medications offer symptomatic relief, they often entail adverse effects and do not address the underlying disease progression.

Phytoconstituents Targeting the Serotonin 5-HT Receptor: Promising Therapeutic Strategies for Neurological Disorders.

The 5-hydroxytryptamine-3 receptor (5-HTR), a subtype of serotonin receptor, is a ligand-gated ion channel crucial in mediating fast synaptic transmission in the central and peripheral nervous systems. This receptor significantly influences various neurological activities, encompassing neurotransmission, mood regulation, and cognitive processing; hence, it may serve as an innovative target for neurological disorders. Multiple studies have revealed promising results regarding the beneficial effects of these phytoconstituents and extracts on conditions such as nausea, vomiting, neuropathic pain depression, anxiety, Alzheimer's disease, cognition, epilepsy, sleep, and dyskinesia via modulation of 5-HTR in the pathophysiology of neurological disorder.

Machine learning-based virtual screening and molecular modelling studies for identification of butyrylcholinesterase inhibitors as anti-Alzheimer's agent.

Butyrylcholinesterase (BChE) is a hydrolase involved in the metabolism and detoxification of specific esters in the blood. It is also implicated in the progression of Alzheimer's disease, a type of dementia. As the disease progresses, the level of BChE tends to increase, opting for a major role as an acetylcholine-degrading enzyme and surpassing the role of acetylcholinesterase.

Centella asiatica improves memory and executive function in middle-aged rats by controlling oxidative stress and cholinergic transmission.

Ethnopharmacological Relevance: Centella asiatica (L.) Urban, is a medicinal herb with rich history of traditional use in Indian subcontinent. This herb has been valued for its diverse range of medicinal properties including memory booster, and also as a folk treatment for skin diseases, wound healing and mild diuretic.

Effect of sulfonamide derivatives of on scopolamine-induced amnesia in rats.

Alzheimer's disease is a neurodegenerative disease responsible for dementia and other neuropsychiatric symptoms. In the present study, compounds and , developed earlier in our laboratory as selective butyrylcholinesterase inhibitors, were tested against scopolamine-induced amnesia to evaluate their pharmacodynamic effect. The efficacy of the compounds was determined by behavioral experiments using the Y-maze and the Barnes maze and neurochemical testing.

Preparation, Characterization, in-vitro and in-vivo Pharmacokinetic Evaluation of Thermostable Dimethyl Fumarate Cocrystals.

Dimethyl fumarate (DMF) is an FDA-approved drug for treating relapsing-remitting multiple sclerosis; but it is susceptible to sublimation leading to its loss during processing. Cocrystals can protect against thermal energy via the interaction of DMF with a coformer via weak forces of interaction. With this hypothesis, we have, for the first time, prepared DMF cocrystals using the solvent evaporation method using coformers like citric acid and succinic acid screened by in-silico predictions and hydrogen bonding properties.

Small size silver nanoparticles loaded with glycoside rich portion of Boerhavia Diffusa Linn. promotes wound healing: in-silico and in-vivo studies.

Silver nanoparticles (Ag-NPs) are increasingly used in various fields, including medicine, owing to their unique physicochemical properties. Due to their smaller size, the contact with biological components is increased, and consequently, it performs better as an antibacterial and antimicrobial. In this study, the authors have focused on the synthesis of small-sized spherical silver nanoparticles (Ag-NPs) by a chemical reduction method using two different capping agents and concentrations of AgNO as a precursor.

Novel Gastroprotective and Thermostable Cocrystal of Dimethyl Fumarate: Its Preparation, Characterization, and and Evaluation.

Crystallization has revolutionized the field of solid-state formulations by modulating the physiochemical and release profile of active pharmaceutical ingredients (APIs). Dimethyl fumarate (DF), an FDA-approved first-line drug for relapsing-remitting multiple sclerosis, has a sublimation problem, leading to loss of the drug during its processing. To tackle this problem, DF cocrystal has been prepared by using solvent evaporation technique using nicotinamide as a coformer, which has been chosen based on predictions and their ability to participate in hydrogen bonding.

Discovery of triazole-bridged aryl adamantane analogs as an intriguing class of multifunctional agents for treatment of Alzheimer's disease.

Alzheimer's disease (AD) is a progressive brain disorder associated with slow loss of brain functions leading to memory failure and modest changes in behavior. The multifactorial neuropathological condition is due to a depletion of cholinergic neurons and accumulation of amyloid-beta (Aβ) plaques. Recently, a multi-target-directed ligand (MTDL) strategy has emerged as a robust drug discovery tool to overcome current challenges.

An Overview of Chemistry, Kinetics, Toxicity and Therapeutic Potential of Boldine in Neurological Disorders.

Boldine is an alkaloid obtained from the medicinal herb Peumus boldus (Mol.) (Chilean boldo tree; boldo) and belongs to the family Monimiaceae. It exhibits a wide range of pharmacological effects such as antioxidant, anticancer, hepatoprotective, neuroprotective, and anti-diabetic properties.

Identification of potential death-associated protein kinase-1 (DAPK1) inhibitors by an integrated ligand-based and structure-based computational drug design approach.

Death-associated protein kinase 1 (DAPK1) is a calcium/calmodulin (Ca/CaM)-dependent serine/threonine kinase that is abundantly expressed in the memory- and cognition-related brain areas. DAPK1 is associated with several pathological hallmarks of Alzheimer's disease (AD); it is an attractive target for designing a novel DAPK1 inhibitor as an effective therapeutic treatment for AD. In the present study, we have used an integrated ligand-based and structure-based drug design method to identify DAPK1 inhibitors.

Identification of novel glucocerebrosidase chaperone for potential treatment of Parkinson's disease: An approach using in silico virtual screening, molecular docking and molecular dynamics, and in vitro studies.

Glucocerebrosidase (GCase), a GBA1 gene-encoded lysosomal enzyme, is a risk factor for Parkinson's disease (PD). Chaperones that increase GCase activity can potentially be disease-modifying agents in PD. To date, none of the registered treatments has demonstrated disease-modifying effects.

Combined ligand-based and structure-based design of PDE 9A inhibitors against Alzheimer's disease.

PDE9 enzyme hydrolyzes cGMP, which is involved in the regulation of synaptic plasticity through the NMDA pathway (a well-known excitotoxic target for AD) via activation of calcium/calmodulin-dependent neuronal NO synthases in the postsynaptic neurons. The inhibition of PDE9 leads to elevated cGMP levels, causing enhanced NMDA signaling and thus contributing to an increase in synaptic plasticity and stabilization. Therefore, it could be considered a pertinent target for AD drug discovery.

Pharmacophore-based virtual screening, molecular docking and molecular dynamics simulations study for the identification of LIM kinase-1 inhibitors.

LIM kinases (LIMKs) are a family of protein kinases involved in the regulation of actin dynamics. There are two isoforms of LIMKs i.e.

Identification of sulfonamide-based butyrylcholinesterase inhibitors using machine learning.

This study reports the designing of BChE inhibitors through machine learning (ML), followed by and evaluations. ML technique was used to predict the virtual hit, and its derivatives were synthesized and characterized. The compounds were evaluated by using various tests and methods.

Generation of wild-type rat Glucocerebrosidase homology modeling: Identification of putative interactions site and mechanism for chaperone using combined in-silico and in-vitro studies.

Disease-modifying treatment strategy for Parkinson's disease (PD) by stabilization of Glucocerebrosidase (GCase) enzyme by chaperones is of particular interest. Wild-type rat is a widely used animal model for PD; however, the in-silico model to elucidate the nature of rat GCase (rGCase)-chaperone interactions, mechanisms, and structural stability is still unavailable. Hence, we have developed pH-dependent rGCase homology models, in-silico (docking and molecular dynamics), and in-vitro techniques (enzyme kinetics and thermal stability) to address this gap.

Cathepsin B-A Neuronal Death Mediator in Alzheimer's Disease Leading to Neurodegeneration.

The lysosomal cysteine protease enzyme, named Cathepsin B, mainly degrades the protein and manages its average turnover in our body. The Cathepsin B active form is mostly present inside the lysosomal part at a cellular level, providing the slightly acidic medium for its activation. Multiple findings on Cathepsin B reveal its involvement in neurons' degeneration and a possible role as a neuronal death mediator in several neurodegenerative diseases.

Identification of sulfonamide based butyrylcholinesterase inhibitors through scaffold hopping approach.

Butyrylcholinesterase (BChE), a hydrolytic enzyme, is responsible for the termination of the action of acetylcholine besides acetylcholinesterase (AChE) in the synaptic cleft of the brain. The alteration in the enzyme level, in patients with the progression of Alzheimer's disease, makes it a therapeutic target. In the present study, we developed BChE inhibitors through scaffold hopping by exploring two previously reported compounds, i.

Development of homology model, docking protocol and Machine-Learning based scoring functions for identification of 's butyrylcholinesterase inhibitors.

Machine learning (ML), an emerging field in drug design, has the potential to predict toxicity, shape-based analysis of inhibitors, scoring function (SF) etc. In the present study, a homology model, docking protocol, and a dedicated SF have been developed to identify the inhibitors of horse butyrylcholinesterase (BChE) enzyme. Horse BChE enzyme has homology with human BChE and is a substitute for the screening of inhibitors.

Cellular and molecular influencers of neuroinflammation in Alzheimer's disease: Recent concepts & roles.

Alzheimer's disease (AD), an extremely common neurodegenerative disorder of the older generation, is one of the leading causes of death globally. Besides the conventional hallmarks i.e.

Classification of beta-site amyloid precursor protein cleaving enzyme 1 inhibitors by using machine learning methods.

The beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) is a transmembrane aspartyl-protease, that cleaves amyloid precursor protein (APP) at the β-site. The sequential proteolytic cleavage of APP, first by β-secretase and then by γ-secretase complex, leads to the production and release of amyloid-β peptide, a pathological hallmark of Alzheimer's disease (AD). BACE1 inhibitors are reported to possess considerable potential in decreasing the level of amyloid-β in brain and preventing the progression of AD.

Improved machine learning scoring functions for identification of Electrophorus electricus's acetylcholinesterase inhibitors.

Structure-based drug design (SBDD) is an important in silico technique, used for the identification of enzyme inhibitors. Acetylcholinesterase (AChE), obtained from Electrophorus electricus (ee), is widely used for the screening of AChE inhibitors. It shares structural homology with the AChE of human and other organisms.

Syringic acid, a novel thyroid hormone receptor-β agonist, ameliorates propylthiouracil-induced thyroid toxicity in rats.

The aim of this study was to evaluate the potential of syringic acid (SA) against propylthiouracil (PTU)-induced hypothyroidism in rats. SA at a prestandardized dose, 50 mg/kg/day, was orally administered to PTU-induced hypothyroid rats for 30 days, and alterations in the levels of serum triiodothyronine (T ), thyroxine (T ), thyrotropin (TSH), alanine transaminase (ALT), and aspartate transaminase (AST); tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6); total cholesterol (CHOL) and triglycerides (TG); hepatic lipid peroxidation (LPO) and antioxidants (superoxide dismutase, catalase, glutathione peroxidase, and glutathione content), as well as histological changes in liver and thyroid were examined. The molecular interactions of the ligand, SA, with thyroid-related protein targets, such as human thyroid hormone receptor β (hTRβ), and thyroid peroxidase (TPO) protein, were studied using molecular docking.

Multifunctional hybrid sulfonamides as novel therapeutic agents for Alzheimer's disease.

A breakthrough in modern medicine, in terms of treatment of Alzheimer's disease, is yet to be seen, as the scene is currently plagued with numerous clinical trial failures. Here, we are exploring multifunctional hybrid sulfonamides for their anti-Alzheimer activity due to the complex nature of the disease. Compound 41 showed significant inhibition of MMP-2 (IC: 18.

Discovery of novel series of 2-substituted benzo[d]oxazol-5-amine derivatives as multi-target directed ligands for the treatment of Alzheimer's disease.

Alzheimer's disease (AD) is associated with multifactorial neuropathological conditions, which include cholinergic deficit, amyloid-beta plaques formation, loss of neuronal plasticity and neuronal death. Treating such multifactorial conditions with a single target directed approach is considered to be inadequate. Accordingly, multi-target directed ligand (MTDL) strategy has been evolved as an auspicious approach for the treatment of AD.