Evidence
ACS Chem Neurosci. 2024 Feb 6. doi: 10.1021/acschemneuro.3c00662. Online ahead of print.
ABSTRACT
The most frequent type of age-related dementia is Alzheimer’s disease. To discover novel therapeutic agents for Alzheimer’s disease, a series of substituted pyrimidine derivatives were synthesized and evaluated for anti-Alzheimer’s activity. All the synthesized compounds were validated by 1HNMR, 13CNMR, and HRMS to assess the structural conformance of the newly synthesized compounds. The synthesized compounds were then evaluated for their in vivo acute toxicity study. Evaluation of acute toxicity showed that none of the synthesized compounds showed toxicity up to 1000 mg/kg. After in vivo acute toxicity studies, the compounds were subjected to behavioral and biochemical studies. Compound N4-(4-chlorophenyl)-N2-(2-(piperidin-1-yl)ethyl)pyrimidine-2,4-diamine 5b (SP-2) displayed an excellent anti-Alzheimer’s profile, while the rest of the compounds showed satisfactory results in comparison to donepezil. Docking studies confirmed the results obtained through in vivo experiments and showed that 5b (SP-2) showed a similar interaction to that of donepezil. Further, in silico molecular property predictions showed that 5b (SP-2) possesses favorable drug-likeness and ADME properties for CNS activity. These results implied that 5b could serve as an appropriate lead molecule for the development of anti-Alzheimer’s agent.
PMID:38320262 | DOI:10.1021/acschemneuro.3c00662
Estimated reading time: 4 minute(s)
Latest: Psychiatryai.com #RAISR4D Evidence
Cool Evidence: Engaging Young People and Students in Real-World Evidence
Real-Time Evidence Search [Psychiatry]
AI Research
Novel Substituted Pyrimidine Derivatives as Potential Anti-Alzheimer’s Agents: Synthesis, Biological, and Molecular Docking Studies
🌐 90 Days
AI Virtual Reality Related Evidence Matrix
- Design and synthesis of novel JNK inhibitors targeting liver pyruvate kinase for the treatment of non-alcoholic fatty liver disease and hepatocellular carcinoma
- Molecular Docking, Synthesis, and Characterization of Furanyl-pyrazolyl acetamide and 2,4-thiazolidinyl-furan-3-carboxamide Derivatives as Neuroinflammatory Protective Agents
- Unveiling new thiazole-clubbed piperazine derivatives as multitarget anti-AD: Design, synthesis, and in silico studies
- Development of novel 9H-carbazole-4H-chromene hybrids as dual cholinesterase inhibitors for the treatment of Alzheimer's disease
- Click-chemistry mediated synthesis of OTBN-1,2,3-Triazole derivatives exhibiting STK33 inhibition with diverse anti-cancer activities
- Investigation of 3-Phenylcoumarin Derivatives as Potential Multi-target Inhibitors for Human Cholinesterases and Monoamine oxidases: A Computational Approach
- Investigation of 3-Phenylcoumarin Derivatives as Potential Multi-target Inhibitors for Human Cholinesterases and Monoamine oxidases: A Computational Approach
- Exploring bi-carbazole-linked triazoles as inhibitors of prolyl endo peptidase via integrated in vitro and in silico study
- Promotion of Water as Solvent in Amination of 4-Chloropyrrolopyrimidines and Related Heterocycles under Acidic Conditions
- Fentanyl-Type Antagonist of the μ-Opioid Receptor: Important Role of Axial Chirality in the Active Conformation
- A review of the ethnopharmacology, phytochemistry, pharmacology, pharmacokinetics and toxicology of Abri Herba (Ji-Gu-Cao)
- Benzofurans as acetylcholinesterase inhibitors for treating Alzheimer's disease: synthesis, in vitro testing, and in silico analysis
- Unlocking bacterial defense: Exploring the potent inhibition of NorA efflux pump by coumarin derivatives in Staphylococcus aureus
- Using Drosophila amyloid toxicity models to study Alzheimer's disease
- 4-Amidophenol Quinone Methide Precursors: Effective and Broad-Scope Nonoxime Reactivators of Organophosphorus-Inhibited Cholinesterases and Resurrectors of Organophosphorus-Aged Acetylcholinesterase
- Therapeutic potential of Bergenin in the management of neurological-based diseases and disorders
- The identification of active compounds and therapeutic properties of fermented and non-fermented red sorghum for the treatment of Alzheimer's dementia
- Multi-target drugs for Alzheimer's disease
- Naphthoquinones and anthraquinones: Exploring their impact on acetylcholinesterase enzyme activity
- Exploring novel indazole derivatives as ASK1 inhibitors: Design, synthesis, biological evaluation and docking studies
- Targeting ASK1 by CS17919 alleviates kidney- and liver-related diseases in murine models
- Targeting ASK1 by CS17919 alleviates kidney- and liver-related diseases in murine models
- α-Glucosidase, butyrylcholinesterase and acetylcholinesterase inhibitory activities of phenolic compounds from Carthamus tinctorius L. flowers: In silico and in vitro studies
- Development of an (18)F-labeled azobenzothiazole tracer for alpha-synuclein aggregates in the brain
- Synthetic Derivatives of Natural ent-Kaurane Atractyligenin Disclose Anticancer Properties in Colon Cancer Cells, Triggering Apoptotic Cell Demise
- Discovery of 3-((4-Benzylpyridin-2-yl)amino)benzamides as Potent GPR52 G Protein-Biased Agonists
- A theoretical screening of phytochemical constituents from Millettia brandisiana as inhibitors against acetylcholinesterase
- Role of Serotonylation and SERT Posttranslational Modifications in Alzheimer's Disease Pathogenesis
- Recent Advances in Fluorescent Theranostics for Alzheimer's Disease: A Comprehensive Survey on Design, Synthesis, and Properties
- Morphological profiling in human neural progenitor cells classifies hits in a pilot drug screen for Alzheimer's disease
- RE104: Synthesis and Activity of a Novel Serotonergic Psychedelic Prodrug of 4-Hydroxy-N,N-diisopropyltryptamine
- Antibiotic discovery with artificial intelligence for the treatment of Acinetobacter baumannii infections
- Pongamol Alleviates Neuroinflammation and Promotes Autophagy in Alzheimer's Disease by Regulating the Akt/mTOR Signaling Pathway
- Exploring the potential of quercetin in Alzheimer's Disease: Pharmacodynamics, Pharmacokinetics, and Nanodelivery systems
- Effect of Natural Osmolytes on Recombinant Tau Monomer: Propensity of Oligomerization and Aggregation
- Protective Effect of Hop Ethyl Acetate Extract on Corticosterone-Induced PC12 and Improvement of Depression-like Behavior in Mice
- Divergent Age-Dependent Conformational Rearrangement within Ab Amyloid Deposits in APP23, APPPS1, and AppNL-F Mice
- Vitamin D, Alzheimer's disease and related dementia
- Prenylated Flavanone Isolated from Dalea Species as a Potential Multitarget-Neuroprotector in an In Vitro Alzheimer's Disease Mice Model
- Chondroitin sulphate modified MoS2 nanoenzyme with multifunctional activities for treatment of Alzheimer's disease
- Clozapine-laden carbon dots delivered to the brain via an intranasal pathway: Synthesis, characterization, ex vivo, and in vivo studies
- Effects of organophosphates on precision-cut kidney slices
- Effect of Cinnamaldehyde Chalcone on Behavior in Adult Zebrafish (Danio rerio): In Silico Approach
- Effect of Cinnamaldehyde Chalcone on Behavior in Adult Zebrafish (Danio rerio): In Silico Approach
- P2Y1 receptor in Alzheimer's disease
- Yeast Platforms for Production and Screening of Bioactive Derivatives of Rauwolscine
- Yeast Platforms for Production and Screening of Bioactive Derivatives of Rauwolscine
- Putamen iron quantification in diseases with neurodegeneration: a meta-analysis of the quantitative susceptibility mapping technique
- Kaempferol efficacy in metabolic diseases: Molecular mechanisms of action in diabetes mellitus, obesity, non-alcoholic fatty liver disease, steatohepatitis, and atherosclerosis
- Benefits of Music Therapy in the Cognitive Impairments of Alzheimer's-Type Dementia: A Systematic Review
- Selection of lansoprazole from an FDA-approved drug library to inhibit the Alzheimer's disease seed-dependent formation of tau aggregates
- Synthesis and biological evaluation of the novel chrysin prodrug for non-alcoholic fatty liver disease treatment
- Oxyresveratrol-b-cyclodextrin mitigates streptozotocin-induced Alzheimer's model cognitive impairment, histone deacetylase activity in rats: in silico & in vivo studies
- Bioassay-guided isolation of anti-inflammatory and antinociceptive metabolites among three Moroccan Juniperus leaves extract supported with in vitro enzyme inhibitory assays
- The role of ω-3 polyunsaturated fatty acids in child development
- Mechanism of action of Sambucus williamsii Hance var. miquelii in the treatment of osteoporosis analyzed by UHPLC-HRMS/MS combined network pharmacology and experimental validation
- Exploring morphological similarity and randomness in Alzheimer's disease using adjacent grey matter voxel-based structural analysis
- Passive immunotherapy for Alzheimer's disease: challenges & future directions
- The Role of PNPLA3_rs738409 Gene Variant, Lifestyle Factors, and Bioactive Compounds in Nonalcoholic Fatty Liver Disease: A Population-Based and Molecular Approach towards Healthy Nutrition
- An insight for the inhibition of anxiolytic and anti-convulsant effects in zebrafish using the curcumins via exploring molecular docking and molecular dynamics simulations
- Prenatal Fluoxetine Exposure Influences Glucocorticoid Receptor-Mediated Activity in the Prefrontal Cortex of Adolescent Rats Exposed to Acute Stress
- Novel Inhibitory Site Revealed by XAP044 Mode of Action on the Metabotropic Glutamate 7 Receptor Venus Flytrap Domain
- Types of memory, dementia, Alzheimer's disease, and their various pathological cascades as targets for potential pharmacological drugs
- Lithium therapy's potential to lower dementia risk and the prevalence of Alzheimer's disease: a meta-analysis
Evidence Blueprint
Novel Substituted Pyrimidine Derivatives as Potential Anti-Alzheimer’s Agents: Synthesis, Biological, and Molecular Docking Studies
☊ AI-Driven Related Evidence Nodes
(recent articles with at least 5 words in title)
More Evidence
Novel Substituted Pyrimidine Derivatives as Potential Anti-Alzheimer’s Agents: Synthesis, Biological, and Molecular Docking Studies
🌐 365 Days
AI Virtual Reality Related Evidence Matrix
- Novel quinazolinone Derivatives: Design, synthesis and in vivo evaluation as potential agents targeting Alzheimer disease
- Design and synthesis of novel JNK inhibitors targeting liver pyruvate kinase for the treatment of non-alcoholic fatty liver disease and hepatocellular carcinoma
- Molecular Docking, Synthesis, and Characterization of Furanyl-pyrazolyl acetamide and 2,4-thiazolidinyl-furan-3-carboxamide Derivatives as Neuroinflammatory Protective Agents
- Computational Studies and Antimicrobial Activity of 1-(benzo[d]oxazol-2-yl)-3,5-Diphenylformazan Derivatives
- Unveiling new thiazole-clubbed piperazine derivatives as multitarget anti-AD: Design, synthesis, and in silico studies
- Development of novel 9H-carbazole-4H-chromene hybrids as dual cholinesterase inhibitors for the treatment of Alzheimer's disease
- Synthesis and biochemical evaluation of 17-N-beta-aminoalkyl-4,5α-epoxynormorphinans
- Click-chemistry mediated synthesis of OTBN-1,2,3-Triazole derivatives exhibiting STK33 inhibition with diverse anti-cancer activities
- Dual Piperidine-Based Histamine H3 and Sigma-1 Receptor Ligands in the Treatment of Nociceptive and Neuropathic Pain
- Development of Pyridothiophene Compounds for PET Imaging of α-Synuclein
- Cannabinoformins: Designing Biguanide-Embedded, Orally Available, Peripherally Selective Cannabinoid-1 Receptor Antagonists for Metabolic Syndrome Disorders
- Investigation of 3-Phenylcoumarin Derivatives as Potential Multi-target Inhibitors for Human Cholinesterases and Monoamine oxidases: A Computational Approach
- Investigation of 3-Phenylcoumarin Derivatives as Potential Multi-target Inhibitors for Human Cholinesterases and Monoamine oxidases: A Computational Approach
- Amyloid Targeting Red Emitting AIE Dots for Diagnostic and Therapeutic Application against Alzheimer's Disease
- Synthesis and Evaluation of Natural and Unnatural Tetrahydrocannabiorcol for Its Potential Use in Neuropathologies
- Exploring bi-carbazole-linked triazoles as inhibitors of prolyl endo peptidase via integrated in vitro and in silico study
- Furofuranoid-Type Lignans and Related Phenolics from Anisacanthus virgularis (Salisb.) Nees with Promising Anticholinesterase and Anti-Ageing Properties: A Study Supported by Molecular Modelling
- Evaluation of Anti-Neuroinflammatory Activity of Isatin Derivatives in Activated Microglia
- Promotion of Water as Solvent in Amination of 4-Chloropyrrolopyrimidines and Related Heterocycles under Acidic Conditions
- Fentanyl-Type Antagonist of the μ-Opioid Receptor: Important Role of Axial Chirality in the Active Conformation
- Metabolic profiling of Alzheimer's disease: Untargeted metabolomics analysis of plasma samples
- A review of the ethnopharmacology, phytochemistry, pharmacology, pharmacokinetics and toxicology of Abri Herba (Ji-Gu-Cao)
- Citronellal as a Promising Candidate for Alzheimer's Disease Treatment: A Comprehensive Study on In Silico and In Vivo Anti-Acetylcholine Esterase Activity
- Design and construction of novel pyridine-pyrimidine hybrids as selective COX-2 suppressors: anti-inflammatory potential, ulcerogenic profile, molecular modeling and ADME/Tox studies
- Pharmacological and Physicochemical Properties Optimization for Dual-Target Dopamine D3 (D3R) and μ-Opioid (MOR) Receptor Ligands as Potentially Safer Analgesics
- A MOR Antagonist with High Potency and Antagonist Efficacy among Diastereomeric C9-Alkyl-Substituted N-Phenethyl-5-(3-hydroxy)phenylmorphans
- Benzofurans as acetylcholinesterase inhibitors for treating Alzheimer's disease: synthesis, in vitro testing, and in silico analysis
- Unlocking bacterial defense: Exploring the potent inhibition of NorA efflux pump by coumarin derivatives in Staphylococcus aureus
- Autophagy Inhibition with Chloroquine Increased Pro-Apoptotic Potential of New Aziridine-Hydrazide Hydrazone Derivatives against Glioblastoma Cells
- Designer Drug, 25D-NBOMe, Has Reinforcing and Rewarding Effects through Change of a Dopaminergic Neurochemical System
- Characterization of (R)- and (S)-[18F]OF-NB1 in Rodents as Positron Emission Tomography Probes for Imaging GluN2B Subunit-Containing N-Methyl-d-Aspartate Receptors
- γ-Secretase Inhibitors Selected by Molecular Docking, to Develop a New Drug Against Alzheimer's Disease
- Psychedelics for Alzheimer's Disease-Related Dementia: Unveiling Therapeutic Possibilities and Pathways
- Using Drosophila amyloid toxicity models to study Alzheimer's disease
- 4-Amidophenol Quinone Methide Precursors: Effective and Broad-Scope Nonoxime Reactivators of Organophosphorus-Inhibited Cholinesterases and Resurrectors of Organophosphorus-Aged Acetylcholinesterase
- Advances in nanoprobes for molecular MRI of Alzheimer's disease
- Identification of an Antagonist Targeting G Protein and β-Arrestin Signaling Pathways of 5-HT7R
- Ferulago angulata Methanolic Extract Protects PC12 Cells Against Beta-amyloid-induced Toxicity
- Concise and Scalable Radiosynthesis of (+)-[18F]MDL100907 as a Serotonin 5-HT2A Receptor Antagonist for PET
- Molecular docking and dynamics simulations revealed the potential inhibitory activity of honey-iQfood ingredients against GSK-3β and CDK5 protein targets for brain health
- Application of P7C3 Compounds to Investigating and Treating Acute and Chronic Traumatic Brain Injury
- Therapeutic potential of oleanolic acid in liver diseases
- Quantitative Assays for Catalytic Photo-Oxygenation of Alzheimer Disease-Related Tau Proteins
- Perceptual Modifying Compounds and Their Potential Therapeutic Applications in Neuropsychiatric Disorders
- Synthesis and Preclinical Evaluation of 22-[18F]Fluorodocosahexaenoic Acid as a Positron Emission Tomography Probe for Monitoring Brain Docosahexaenoic Acid Uptake Kinetics
- Deciphering the putative bioactive metabolites and the underlying mechanism of Juniperus horizontalis Moench (Creeping juniper) in the treatment of inflammation using network pharmacology and molecular docking
- Exploring antidiabetic potential of a polyherbal formulation Madhurakshak Activ: An in vitro and in silico study
- Therapeutic potential of Bergenin in the management of neurological-based diseases and disorders
- The identification of active compounds and therapeutic properties of fermented and non-fermented red sorghum for the treatment of Alzheimer's dementia
- Multi-target drugs for Alzheimer's disease
- Naphthoquinones and anthraquinones: Exploring their impact on acetylcholinesterase enzyme activity
- Exploring novel indazole derivatives as ASK1 inhibitors: Design, synthesis, biological evaluation and docking studies
- Synthesis, computational simulations and biological evaluation of new dual 5HT1A/5HT7 receptor ligands based on purine-2,6-dione scaffold
- Synthetic Anti-Cocaine Nanoaccine Successfully Prevents Cocaine-Induced Hyperlocomotion
- Targeting ASK1 by CS17919 alleviates kidney- and liver-related diseases in murine models
- Targeting ASK1 by CS17919 alleviates kidney- and liver-related diseases in murine models
- Evolution of Markers Involved in the Fresh Mushroom Off-Flavor in Wine During Alcoholic Fermentation
- α-Glucosidase, butyrylcholinesterase and acetylcholinesterase inhibitory activities of phenolic compounds from Carthamus tinctorius L. flowers: In silico and in vitro studies
- Design, synthesis, and analgesia evaluation of novel Transient Receptor Potential Vanilloid 1 (TRPV1) agonists modified from Cannabidiol (CBD)
- Novel compound inhibits glycolysis, proteotoxicity, inflammation, and impairments in animal models of Alzheimer's, Huntington's, and stroke: Aging as a consequence of glycolysis
- Development of an (18)F-labeled azobenzothiazole tracer for alpha-synuclein aggregates in the brain
- Hydrodynamic Control of Alzheimer Aβ Fibrillation with Glucosaminic Acid Containing Click-Cyclized β-Bodies
- Molecular cross-talk between long COVID-19 and Alzheimer's disease
- Dissecting the Relationship Between Neuropsychiatric and Neurodegenerative Disorders