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
Add to Google Keep
Estimated reading time: 4 minute(s)
Latest: Psychiatryai.com #RAISR4D
Real-Time Evidence Search [Psychiatry]
Novel Substituted Pyrimidine Derivatives as Potential Anti-Alzheimer’s Agents: Synthesis, Biological, and Molecular Docking Studies
🌐 90 Days
VR Related Evidence Matrix
- Molecular Docking, Synthesis, and Characterization of Furanyl-pyrazolyl acetamide and 2,4-thiazolidinyl-furan-3-carboxamide Derivatives as Neuroinflammatory Protective Agents
- Development of Pyridothiophene Compounds for PET Imaging of α-Synuclein
- 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
- Promotion of Water as Solvent in Amination of 4-Chloropyrrolopyrimidines and Related Heterocycles under Acidic Conditions
- 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
- Psychedelics for Alzheimer's Disease-Related Dementia: Unveiling Therapeutic Possibilities and Pathways
- γ-Secretase Inhibitors Selected by Molecular Docking, to Develop a New Drug Against Alzheimer's Disease
- Using Drosophila amyloid toxicity models to study Alzheimer's disease
- 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
- Therapeutic potential of oleanolic acid in liver diseases
- Perceptual Modifying Compounds and Their Potential Therapeutic Applications in Neuropsychiatric Disorders
- Molecular cross-talk between long COVID-19 and Alzheimer's disease
- Natural compounds mitigate mycotoxins-induced neurotoxicity by modulating oxidative tonus: in vitro and in vivo insights - a review
- Recent Advances in Fluorescent Theranostics for Alzheimer's Disease: A Comprehensive Survey on Design, Synthesis, and Properties
- New approach for early and specific Alzheimer disease diagnosis from different plasma biomarkers
- Morphological profiling in human neural progenitor cells classifies hits in a pilot drug screen for Alzheimer's disease
- A Spontaneous Assembling Lipopeptide Nanoconjugate Transporting the Anthracycline Drug N-Benzyladriamycin-14-valerate for Personalized Therapy of Ewing Sarcoma
- Hybrid Allosteric Modulators of M1 Muscarinic Receptors Enhance Acetylcholine Efficacy and Decrease Locomotor Activity and Turning Behaviors in Zebrafish
- Pyrazoline Derivatives as Promising MAO-A Targeting Antidepressants: An Update
- Exploring the potential of quercetin in Alzheimer's Disease: Pharmacodynamics, Pharmacokinetics, and Nanodelivery systems
- Novel Benzofuran Derivatives Induce Monoamine Release and Substitute for the Discriminative Stimulus Effects of 3,4-Methylenedioxymethamphetamine
- Effect of Natural Osmolytes on Recombinant Tau Monomer: Propensity of Oligomerization and Aggregation
- 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
- Spatial Neurolipidomics at the Single Amyloid-β Plaque Level in Postmortem Human Alzheimer's Disease Brain
- Prenylated Flavanone Isolated from Dalea Species as a Potential Multitarget-Neuroprotector in an In Vitro Alzheimer's Disease Mice Model
- GABA-Transaminase: A Key Player and Potential Therapeutic Target for Neurological Disorders
- Alzheimer's Disease and Suicide: An Integrative Literature Review
- Potential of the Blue Calm® food supplement in the treatment of alcohol withdrawal-induced anxiety in adult zebrafish (Danio rerio)
- Conventional and multi-omics assessments of subacute inhalation toxicity due to propylene glycol and vegetable glycerin aerosol produced by electronic cigarettes
- Memantine versus Ginkgo biloba Extract: A Comparative Study on Cognitive Dysfunction Treatment in a Novel Rat Model
- Types of memory, dementia, Alzheimer's disease, and their various pathological cascades as targets for potential pharmacological drugs
- Multi-Omic Blood Biomarkers as Dynamic Risk Predictors in Late-Onset Alzheimer's Disease
- Racial/Ethnic Disparities in Use of Angiotensin II Receptor Type 2/4 Stimulatory Vs. Inhibitory Antihypertensive Among Hypertensive Adults in the USA
- Ischemia-Reperfusion Programming of Alzheimer's Disease-Related Genes-A New Perspective on Brain Neurodegeneration after Cardiac Arrest
- Prenatal Fluoxetine Exposure Influences Glucocorticoid Receptor-Mediated Activity in the Prefrontal Cortex of Adolescent Rats Exposed to Acute Stress
- Exploring the anti-ferroptosis mechanism of Kai-Xin-San against Alzheimer's disease through integrating network pharmacology, bioinformatics, and experimental validation strategy in vivo and in vitro
- New horizons in the diagnosis and management of Alzheimer's Disease in older adults
- Flavonoids and Alzheimer's disease: reviewing the evidence for neuroprotective potential
- Ribonucleotide reductase inhibition improves the symptoms of a Caenorhabditis elegans model of Alzheimer's Disease
- Spectroscopic and Computational Study of ZnCl2-Methanol Low-Melting-Temperature Mixtures
- Genetic deletion of astrocytic calcineurin B1 prevents cognitive impairment and neuropathology development in acute and chronic mouse models of Alzheimer's disease
- Toxicologic Pathology Forum Opinion: Rational Approaches to Expanded Neurohistopathology Evaluation for Nonclinical General Toxicity Studies and Juvenile Animal Studies
- Network-based identification and mechanism exploration of active ingredients against Alzheimer's disease via targeting endoplasmic reticulum stress from traditional chinese medicine
- Ferroptosis inhibitors reduce celastrol toxicity and preserve its insulin sensitizing effects in insulin resistant HepG2 cells
- Exploring the Function of (+)-Naltrexone Precursors: Their Activity as TLR4 Antagonists and Potential in Treating Morphine Addiction
- Therapeutic potential of stilbenes in neuropsychiatric and neurological disorders: A comprehensive review of preclinical and clinical evidence
- Is Alzheimer disease a disease?
- Pharmacology of bioactive compounds from plant extracts for improving non-alcoholic fatty liver disease through endoplasmic reticulum stress modulation: A comprehensive review
- Memory Circuits in Dementia: The Engram, Hippocampal Neurogenesis and Alzheimer's disease
- Ethanol extracts of Isochrysis zhanjiangensis alleviate acute alcoholic liver injury and modulate intestinal bacteria dysbiosis in mice
- SWOG 1609 cohort 48: anti-CTLA-4 and anti-PD-1 for advanced gallbladder cancer
- Apolar Extracts of St. John's Wort Alleviate the Effects of β-Amyloid Toxicity in Early Alzheimer's Disease
- Extract of Silphium perfoliatum L. improve lipid accumulation in NAFLD mice by regulating AMPK/FXR signaling pathway
- Intranasal administration of the essential oil from Perillae Folium ameliorates social defeat stress-induced behavioral impairments in mice
- Phenibut: Review and Pharmacologic Approaches to Treating Withdrawal
- AI in Pharma: Transforming Drug Discovery and Strategic Management with MYC-Modulating Compounds and BET Protein Inhibitors
- Alterations of Structural Network Efficiency in Early-Onset and Late-Onset Alzheimer's Disease
- Amylin in Alcohol Addiction: A Potential New Treatment Target or an Adjuvant to Other Treatments?
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)
Save Evidence Blueprint
Save as PDF
Novel Substituted Pyrimidine Derivatives as Potential Anti-Alzheimer’s Agents: Synthesis, Biological, and Molecular Docking Studies
🌐 365 Days
VR Related Evidence Matrix
- Novel quinazolinone Derivatives: Design, synthesis and in vivo evaluation as potential agents targeting Alzheimer disease
- 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
- Synthesis and biochemical evaluation of 17-N-beta-aminoalkyl-4,5α-epoxynormorphinans
- 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
- 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
- Metabolic profiling of Alzheimer's disease: Untargeted metabolomics analysis of plasma samples
- STOP-AD portal: Selecting the optimal pharmaceutical for preclinical drug testing in Alzheimer's disease
- 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
- 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
- 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
- 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
- Psychedelics for Alzheimer's Disease-Related Dementia: Unveiling Therapeutic Possibilities and Pathways
- γ-Secretase Inhibitors Selected by Molecular Docking, to Develop a New Drug Against Alzheimer's Disease
- 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
- Using Drosophila amyloid toxicity models to study Alzheimer's disease
- Advances in nanoprobes for molecular MRI of Alzheimer's disease
- New Meloxicam Derivatives-Synthesis and Interaction with Phospholipid Bilayers Measured by Differential Scanning Calorimetry and Fluorescence Spectroscopy
- Identification of an Antagonist Targeting G Protein and β-Arrestin Signaling Pathways of 5-HT7R
- Molecular docking and dynamics simulations revealed the potential inhibitory activity of honey-iQfood ingredients against GSK-3β and CDK5 protein targets for brain health
- 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
- Application of P7C3 Compounds to Investigating and Treating Acute and Chronic Traumatic Brain Injury
- Synthesis and Characterization of ZnO Nanoparticles Derived from Biomass (Sisymbrium Irio) and Assessment of Potential Anticancer Activity
- 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
- Effects and mechanism of action of Chrysanthemum morifolium (Jinsi Huangju) on hyperlipidemia and non-alcoholic fatty liver disease
- 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
- Tripeptides conjugated with thiosemicarbazones: new inhibitors of tyrosinase for cosmeceutical use
- Emerging Nanotechnology for the Treatment of Alzheimer's Disease
- Synthesis, computational simulations and biological evaluation of new dual 5HT1A/5HT7 receptor ligands based on purine-2,6-dione scaffold
- Quantitation of Brain and Blood Glutathione and Iron in Healthy Age Groups Using Biophysical and In Vivo MR Spectroscopy: Potential Clinical Application
- Promising Schiff bases in antiviral drug design and discovery
- Synthetic Anti-Cocaine Nanoaccine Successfully Prevents Cocaine-Induced Hyperlocomotion
- Case report: Identification of AP-238 and 2-fluorodeschloroketamine in internet available powder samples sold as bucinnazine
- Design, synthesis, and analgesia evaluation of novel Transient Receptor Potential Vanilloid 1 (TRPV1) agonists modified from Cannabidiol (CBD)
- Evolution of Markers Involved in the Fresh Mushroom Off-Flavor in Wine During Alcoholic Fermentation
- Molecular cross-talk between long COVID-19 and Alzheimer's disease
- Novel compound inhibits glycolysis, proteotoxicity, inflammation, and impairments in animal models of Alzheimer's, Huntington's, and stroke: Aging as a consequence of glycolysis
- Hydrodynamic Control of Alzheimer Aβ Fibrillation with Glucosaminic Acid Containing Click-Cyclized β-Bodies
- Dissecting the Relationship Between Neuropsychiatric and Neurodegenerative Disorders
- Natural compounds mitigate mycotoxins-induced neurotoxicity by modulating oxidative tonus: in vitro and in vivo insights - a review
- A Combin aed Ligand- and Structure-Based Virtual Screening To Identify Novel NaV1.2 Blockers: In Vitro Patch Clamp Validation and In Vivo Anticonvulsant Activity
- Recent Advances in Fluorescent Theranostics for Alzheimer's Disease: A Comprehensive Survey on Design, Synthesis, and Properties
- New approach for early and specific Alzheimer disease diagnosis from different plasma biomarkers
- Morphological profiling in human neural progenitor cells classifies hits in a pilot drug screen for Alzheimer's disease
- A Spontaneous Assembling Lipopeptide Nanoconjugate Transporting the Anthracycline Drug N-Benzyladriamycin-14-valerate for Personalized Therapy of Ewing Sarcoma
- All-Hydrocarbon Stapled Peptide Multifunctional Agonists at Opioid and Neuropeptide FF Receptors: Highly Potent, Long-Lasting Brain Permeant Analgesics with Diminished Side Effects
- Hybrid Allosteric Modulators of M1 Muscarinic Receptors Enhance Acetylcholine Efficacy and Decrease Locomotor Activity and Turning Behaviors in Zebrafish