Combined Experimental and Computational Investigations of 4‐Amino‐2‐Chloro‐6,7‐Dimethoxyquinazoline as Potential Anti‐Alzheimer Agent DOI

Karthikeyan Asokan,

Karthik Nallasamy,

S. Sivaraman

и другие.

International Journal of Quantum Chemistry, Год журнала: 2024, Номер 124(24)

Опубликована: Дек. 10, 2024

ABSTRACT Alzheimer's disease (AD) is a neurodegenerative condition that leads to the deterioration of brain cells, resulting in memory loss, thinking, and executive skills. In this work, 4‐amino‐2‐chloro‐6,7‐dimethoxyquinazoline (ACDQ) has been studied using 6–311++G(d,p) B3LYP functional density theory (DFT) approach utilizing basis set. Geometry optimization fundamental vibrational frequencies are calculated above method. The spectroscopic investigations such as FT‐IR, FT‐Raman, UV–Vis spectra performed on selected compound. time‐dependent DFT calculations gas water phases determine electronic properties energy gap same Charge distributions have used illustrate between highest occupied lowest unoccupied molecular orbitals. Mulliken population analysis atomic charges ACDQ. From natural bond orbital analysis, it observed there significant electron delocalization ACDQ due presence intramolecular interactions. To evaluate ACDQ's anti‐Alzheimer potential, docking simulation assess its structural stability biological activity against proteins associated with disease. Our study revealed that, strong interaction 4EY7 protein binding −8.1 kcal mol −1 . Additionally, metrics root mean square deviation (RMSD), fluctuation (RMSF), radius gyration considered ( R g ) were computed dynamics simulations protein–ligand interaction. Studies ADMET prediction also carried out. findings current support potential an effective lead therapeutic for

Язык: Английский

Lead optimization based design, synthesis, and pharmacological evaluation of quinazoline derivatives as multi-targeting agents for Alzheimer's disease treatment DOI
Akash Verma,

Digambar Kumar Waiker,

Neha Singh

и другие.

European Journal of Medicinal Chemistry, Год журнала: 2024, Номер 271, С. 116450 - 116450

Опубликована: Апрель 27, 2024

Язык: Английский

Процитировано

6
Harnessing the Therapeutic Potential of Peptides for Synergistic Treatment of Alzheimer’s Disease by Targeting Aβ Aggregation, Metal-Mediated Aβ Aggregation, Cholinesterase, Tau Degradation, and Oxidative Stress DOI
Kamaljot Singh, Anupamjeet Kaur, Bhupesh Goyal

и другие.

ACS Chemical Neuroscience, Год журнала: 2024, Номер 15(14), С. 2545 - 2564

Опубликована: Июль 9, 2024

Alzheimer's disease (AD) is a progressive multifaceted neurodegenerative and remains formidable global health challenge. The current medication for AD gives symptomatic relief and, thus, urges us to look alternative disease-modifying therapies based on multitarget directed approach. Looking at the remarkable progress made in peptide drug development last decade benefits associated with peptides, they offer valuable chemotypes [multitarget ligands (MTDLs)] as therapeutics. This review recapitulates developments harnessing peptides MTDLs combating by targeting multiple key pathways involved disease's progression. hold immense potential represent convincing avenue pursuit of novel While hurdles remain, ongoing research offers hope that may eventually provide approach combat AD.

Язык: Английский

Процитировано

5
Discovery of novel hybrid tryptamine-rivastigmine molecules as potent AChE and BChE inhibitors exhibiting multifunctional properties for the management of Alzheimer’s disease DOI
Gauri Shankar, Prabhat Kumar,

Sanskriti Rai

и другие.

European Journal of Medicinal Chemistry, Год журнала: 2024, Номер 283, С. 117066 - 117066

Опубликована: Ноя. 27, 2024

Язык: Английский

Процитировано

4
Current pharmacophore based approaches for the development of new anti-Alzheimer’s agents DOI
Prachi Sharma,

Sunil Sharma,

Yogesh Yadav

и другие.

Bioorganic & Medicinal Chemistry, Год журнала: 2024, Номер 113, С. 117926 - 117926

Опубликована: Сен. 13, 2024

Язык: Английский

Процитировано

3
Exploring Quinazoline as a Scaffold for Developing Novel Therapeutics in Alzheimer’s Disease DOI Creative Commons
Qais Abualassal, Zead Abudayeh,

Ala’ Yahya Sirhan

и другие.

Molecules, Год журнала: 2025, Номер 30(3), С. 555 - 555

Опубликована: Янв. 26, 2025

Quinazoline, a privileged scaffold in medicinal chemistry, offers promising potential the synthesis of anti-Alzheimer’s disease (AD) drugs. This heterocyclic compound, characterized by its fused benzene and pyrimidine rings, enables design multifunctional agents targeting AD pathology. The drug-like aspects pharmaceutical features quinazoline derivatives have to give rise various therapeutic is progressive neurodegenerative condition marked memory decline, cognitive deterioration, language disorders. Given complexity multifaceted nature, there pressing need discover multi-target drugs effectively address this debilitating disorder. A comprehensive literature review has demonstrated that exhibit wide range for AD. These compounds function as inhibitors cholinesterases, β-amyloid aggregation, oxidative stress, tau protein, among other protective effects. Here, we highlight most significant recent research on quinazoline-based anti-AD agents, aiming support development discovery novel treatments

Язык: Английский

Процитировано

0
Donepezil-Based Rational Design of N-Substituted Quinazolinthioacetamide Candidates as Potential Acetylcholine Esterase Inhibitors for the Treatment of Alzheimer’s Disease: In vitro and In vivo Studies DOI
Ahmed A. Al‐Karmalawy, Ahmed F. Mohamed, Heba Nasr Shalaby

и другие.

RSC Medicinal Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Donepezil-based rational design of N -substituted quinazoline tethered thioacetamide as potential acetylcholine esterase inhibitors for the treatment Alzheimer's disease.

Язык: Английский

Процитировано

0
Tryptophan Metabolism Through the Kynurenine Pathway in Glial Cells DOI Creative Commons

Deivison Silva Argolo,

Lucas Matheus Gonçalves de Oliveira, Gilles J. Guillemin

и другие.

Neuroglia, Год журнала: 2025, Номер 6(1), С. 14 - 14

Опубликована: Март 12, 2025

The central nervous system (CNS) relies on complex and dynamic interactions between neurons glial cells. Among cells, astrocytes regulate the chemical environment surrounding supply essential nutrients for brain metabolism whereas microglia, resident macrophages of CNS, play critical roles in homeostasis, defense, responses to injury. Both microglia contribute regulation excitotoxicity inflammation mediated by tryptophan (Trp) via kynurenine pathway. Trp generates several bioactive metabolites, including quinolinic acid (QUIN) kynurenic (KYNA), which have opposing effects. QUIN, produced activated acts as an agonist NMDA receptors; excessive stimulation these receptors can lead neuronal death. Conversely, KYNA, primarily 2,3-aminotransferases (KAT), receptor antagonist, conferring neuroprotection mitigating excitotoxicity. Dysregulation is implicated many neurodegenerative diseases such Alzheimer’s disease, Parkinson’s multiple sclerosis amyotrophic lateral sclerosis, well various neuropsychiatric disorders. This review examines cellular molecular mechanisms underlying highlighting unique contributions each phenotype, implications CNS pathologies, potential biomarkers therapeutic targets restoring homeostasis preventing disease progression.

Язык: Английский

Процитировано

0
Multitarget Compounds Designed for Alzheimer, Parkinson, and Huntington Neurodegeneration Diseases DOI Creative Commons

Eleftheria-Emmanouela Katsoulaki,

Dimitrios Dimopoulos, Dimitra Hadjipavlou‐Litina

и другие.

Pharmaceuticals, Год журнала: 2025, Номер 18(6), С. 831 - 831

Опубликована: Июнь 1, 2025

Multitarget drugs are molecules with the ability to act simultaneously on different targets at same time, and they have been evaluated in last decade as a powerful tool development of promising therapeutics for neurodegenerative diseases. This is very useful multifactorial diseases such Alzheimer’s, Parkinson’s, Huntington’s diseases, group neurological disorders that induce neurodegeneration neuroinflammation. Successful drug design depends an interdisciplinary collaborative approach. The complexity above pathologies has clearly demonstrated single-target inadequate achieve successful therapeutic result. Furthermore, hitting more than one biological target exhibit also safer profile. In this review, we present comprehensive knowledge recent research multitarget synthetic approaches confront

Язык: Английский

Процитировано

0
Spectroscopic, DFT, In Silico, and Estimation of Biological Activity of 2,4‐Dichloro‐6,7‐Dimethoxyquinazoline as a Potential Anti‐Alzheimer's Disease Therapeutic Agent DOI Creative Commons

Karthikeyan Asokan,

S. Sivaraman,

Karthik Nallasamy

и другие.

International Journal of Quantum Chemistry, Год журнала: 2024, Номер 125(1)

Опубликована: Дек. 30, 2024

ABSTRACT Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by progressive cognitive and behavioral decline. In this study, 2,4‐dichloro‐6,7‐dimethoxyquinazoline (DCDQ) was extensively analyzed using combination of spectroscopic computational approaches. Geometric parameters vibrational modes were computed DFT/B3LYP/6‐311++G(d,p), experimental FT‐IR, FT‐Raman, UV–vis spectrum confirmed the compound's structural properties. Time‐dependent DFT (TD‐DFT) calculations provided insights into electronic structure, including HOMO‐LUMO energies global reactivity descriptors. Molecular electrostatic potential (MEP) analysis Mulliken population studies identified reactive sites bonding characteristics, while NBO revealed significant hyperconjugative interactions contributing to stability. Advanced topological analyses (ELF, LOL, NCI, RDG) QTAIM performed Multiwfn software explore electron density distribution. Biological relevance established through molecular docking studies, which highlighted strong binding affinity DCDQ with 4EY7 protein (binding energy: −8.2 kcal/mol), suggesting its as potent acetylcholinesterase (AChE) inhibitor. dynamics simulations further validated stability protein‐ligand interaction. ADMET predictions also supported favorable pharmacokinetic safety profiles DCDQ. These findings collectively demonstrate promising lead compound for treatment disease, offering solid foundation future therapeutic development.

Язык: Английский

Процитировано

1
Highly Efficient Catalysis of Pyridinium p‐Toluenesulfonate (PPTS): Two Facile One‐Pot Protocols for the Synthesis of 2,3‐Disubstituted Quinazolinone Scaffolds DOI Open Access

Yakkanti Chiranjeevi,

Lakinani Vaikunta Rao,

Akula Raghunadh

и другие.

ChemistrySelect, Год журнала: 2024, Номер 9(38)

Опубликована: Окт. 1, 2024

Abstract Two different one‐pot synthetic protocols have been developed for obtaining 2,3‐disubstituted quinazolin‐4(3 H )‐ones using pyridinium p ‐toluenesulfonate (PPTS) as catalyst. The two‐component reaction involves isatoic anhydride and N‐acetyl amine whereas the three‐component use anhydride, aryl β‐diketone in Toluene under classical heating at 80–100 °C to afford good yields. reactions are compatible with various substituted aryl/alkyl amines.

Язык: Английский

Процитировано

0