In Silico Exploration of APOE4 Inhibitors: Molecular Docking and ADMET Profiling for Alzheimer's Therapy DOI Creative Commons

Sehrish Shafique,

Muhammad Saud Tabish,

Hafiz Muhammad Haseeb Khaliq

et al.

Journal of Health and Rehabilitation Research, Journal Year: 2024, Volume and Issue: 4(1), P. 652 - 658

Published: Feb. 13, 2024

Background: Alzheimer's disease (AD), a prevalent neurodegenerative disorder, poses significant challenges to healthcare systems worldwide. The aggregation of Amyloid-β peptide and the presence apolipoprotein E4 (apoE4) are recognized as central factors in AD pathogenesis. Despite availability FDA-approved drugs, there remains dire need for more effective targeted treatments combat this disease. advent silico methodologies offers promising avenue accelerating drug discovery process, providing cost-effective efficient means screen potential therapeutic agents. Objective: This study aimed identify evaluate inhibitors apoE4 using methods. By targeting interaction domain apoE4, sought discover compounds capable reducing beta-amyloid aggregation, thus offering novel approach therapy. Methods: Computational techniques, including Lipinski Rule Five ADMET filtering, were employed dataset 80 chemical retrieved from NCBI database. Molecular docking was performed assess binding affinities orientations utilizing Phyre2 3D structure prediction AutoDock Vina simulations. selection criteria lead based on their energy, hydrogen bonding interactions, compliance with drug-like properties. Results: Out initial screened, 15 excluded Five, an additional 43 deemed unsuitable following analysis. identified two compounds, taxifolin luteolin, exhibiting superior showing lowest energy -7.4 kcal/mol highest number bonds one its conformations. Conclusion: successfully leveraged methods luteolin potent highlighting computational developing therapies. These findings pave way future experimental validation clinical trials efficacy safety these treating

Language: Английский

“In-Water” Three-Component One-Pot Reaction for the Facile Synthesis of Densely Functionalized 2,3-Dihydro-1H-pyrrol-2-ols and Mechanistic Insight DOI

Saigal Saigal,

Nallakantham Sudheer,

Subash C. Sahoo

et al.

ACS Sustainable Chemistry & Engineering, Journal Year: 2024, Volume and Issue: 12(35), P. 13336 - 13351

Published: Aug. 22, 2024

An environmentally friendly multicomponent reaction strategy for the synthesis of functionally rich all-carbon substituted 2,3-dihydro-1H-pyrrol-2-ols "in-water" at room temperature has been reported. Water plays an indispensable role in presence readily available catalytic surfactants sodium dioctylsulfosuccinate and dodecyl sulfate to effectuate transformation, as proved by inferior results obtained organic solvents. A wide display substrate scope functional group compatibility permits diversity generation a mild operationally simple fashion. High product yields, fast rate, recoverability/recyclability catalysts, high TON/TOF, ease purification final products filtration, AE values, excellent E-factor count with score low possible highlight "greenness" this approach. Feasibility "gram-scale" synthetic elaboration offer notable advantages. The mechanistic understanding intercepting labile "imine" intermediate realized through sequence imine formation Mannich-type followed intramolecular N-cyclization.

Language: Английский

Citations

2
New Class of Thienopyridines: Design, Synthesis, Antimicrobial Activity and Molecular Docking Study DOI
Azhaar T. Alsaggaf, Mostafa Sayed,

Ahmed A . Dewan

et al.

Journal of Molecular Structure, Journal Year: 2024, Volume and Issue: 1323, P. 140741 - 140741

Published: Nov. 14, 2024

Language: Английский

Citations

2
A Computational Approach for the Discovery of Novel DNA Methyltransferase Inhibitors DOI Creative Commons
Eftichia Kritsi, Paris Christodoulou, Thalia Tsiaka

et al.

Current Issues in Molecular Biology, Journal Year: 2024, Volume and Issue: 46(4), P. 3394 - 3407

Published: April 16, 2024

Nowadays, the explosion of knowledge in field epigenetics has revealed new pathways toward treatment multifactorial diseases, rendering key players epigenetic machinery focus today’s pharmaceutical landscape. Among enzymes, DNA methyltransferases (DNMTs) are first studied as inhibition targets for cancer treatment. The increasing clinical interest DNMTs led to advanced experimental and computational strategies search novel DNMT inhibitors. Considering importance a promising trend, present study attempted discover inhibitors natural origin against using combination structure ligand-based approaches. Particularly, pharmacophore-based virtual screening was performed, followed by molecular docking dynamics simulations order establish an accurate robust selection methodology. Our protocol prioritized five natural-derived compounds, derivatives coumarins, flavones, chalcones, benzoic acids, phenazine, bearing completely diverse chemical scaffolds from FDA-approved “Epi-drugs”. Their total inhibitory activity evaluated, revealing results derived hits with ranging within 30–45% at 100 µM tested compounds.

Language: Английский

Citations

1
Machine Learning Techniques for Predicting Drug-Related Side Effects: A Scoping Review DOI Creative Commons
Esmaeel Toni, Haleh Ayatollahi,

Reza Abbaszadeh

et al.

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(6), P. 795 - 795

Published: June 17, 2024

Background: Drug safety relies on advanced methods for timely and accurate prediction of side effects. To tackle this requirement, scoping review examines machine-learning approaches predicting drug-related effects with a particular focus chemical, biological, phenotypical features. Methods: This was in which comprehensive search conducted various databases from 1 January 2013 to 31 December 2023. Results: The results showed the widespread use Random Forest, k-nearest neighbor, support vector machine algorithms. Ensemble methods, particularly random forest, emphasized significance integrating chemical biological features Conclusions: article considering variety features, datasets, learning algorithms Forest best performance combining improved prediction. suggested that techniques have some potential improve drug development trials. Future work should specific feature types, selection techniques, graph-based even better

Language: Английский

Citations

1
The Role of Asymmetric Flow Field-Flow Fractionation in Drug Development – From Size Separation to Advanced Characterization DOI
Klaus Richter,

Angelika Reichel,

Valerija Vezočnik

et al.

Journal of Chromatography A, Journal Year: 2024, Volume and Issue: 1739, P. 465542 - 465542

Published: Nov. 20, 2024

Language: Английский

Citations

1
Drug Design for Alzheimer’s Disease: Biologics vs. Small Molecules DOI
Donald F. Weaver

Current Alzheimer Research, Journal Year: 2023, Volume and Issue: 20(12), P. 821 - 826

Published: Dec. 1, 2023

There shall probably be no "magic bullet" for Alzheimer's; rather, we should pursuing a shotgun blast" that will target multiple complementary therapeutic receptors. Although protein misfolding/oligomerization one of these targets, this alone is insufficient and require the co-administration other entities engaging such as immunopathy, gliopathy, mitochondriopathy, synaptotoxicity or others. polypharmacy emerging preferred route, many questions remain unanswered. Should cocktail biologics, concoction small molecules, judicious combination both? Biologics molecule drugs display both strengths weaknesses. When addressing disease complex globally important Alzheimer's, there room continuing development classes. Each has much to offer, when used with their advantages disadvantages in clear focus, an ultimate solution contributions from both.

Language: Английский

Citations

2
Development of Teaching Module for the Merdeka Curriculum with Nuances Critical Reasoning for Elementary School Students DOI Creative Commons

Angelina Angelina,

Bistari Bistari,

Siti Halidjah

et al.

Jurnal Paedagogy, Journal Year: 2024, Volume and Issue: 11(3), P. 580 - 580

Published: July 15, 2024

This research aims to develop a teaching module for the Merdeka Curriculum with nuances of critical reasoning elementary school students. It does this by outlining validity level assessed from module's suitability aspect, language aspects, and empirical practicality module. study used development method 4D model, which involved definition, design, development, dissemination. The instruments in included validation sheets, interviews, teacher student questionnaires, field trials, trial observation checklists. Data analysis techniques qualitative content descriptive statistics. findings demonstrated that three four stages, define, were completed construct curriculum analysis, needs learning outcomes material are during define step. Designing instructional modules satisfy requirements viability, correctness, clarity, attractive presentation is design stage process. Teaching products put through testing, procedures, checks complete stage. average percentage component appropriateness aspect 4.87 4.81, respectively, very valid criteria. Based on answer questionnaires (4.6 practical criteria) response (4.2 criteria), was determined. these results, practical, so it qualifies as feasible quality product.

Language: Английский

Citations

0
The beneficial effects of lupeol on particulate matter–mediated pulmonary inflammation DOI
Sang‐Hee Cho, Dong Ho Park, Eui Kyun Park

et al.

Food and Chemical Toxicology, Journal Year: 2024, Volume and Issue: 191, P. 114893 - 114893

Published: July 26, 2024

Language: Английский

Citations

0
An Optimization Method for Drug Design Based on Molecular Features DOI
Xuan Liu,

Xiaoli Lin,

Fengli Zhou

et al.

Lecture notes in computer science, Journal Year: 2024, Volume and Issue: unknown, P. 27 - 36

Published: Jan. 1, 2024

Language: Английский

Citations

0
The Role of –OEt Substituents in Molybdenum-Assisted Pentathiepine Formation—Access to Diversely Functionalized Azines DOI Creative Commons

Roberto Tallarita,

Lukas M. Jacobsen,

Siva Sankar Murthy Bandaru

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(16), P. 3806 - 3806

Published: Aug. 11, 2024

1,2,3,4,5-pentathiepines (PTEs) are naturally occurring polysulfides of increasing scientific interest based on their identified pharmacological activities. Artificial PTEs with N-heterocyclic backbones efficiently synthesized via mediation by a molybdenum–oxo-bistetrasulfido complex. A common feature all precursor alkynes successfully used to date in this reaction is the presence –CH(OEt)2 group since previously postulated mechanism requires one OEt– as leaving group, and second must become transient ethoxonium moiety. This raised question whether there really need for two, maybe only one, or possibly even zero ethoxy substituents. research problem was systematically addressed respective variations precursor-alkyne derivatives employing related allene species. It found that total absence substituents prevents formation entirely, while single results possibility distinctly functionalize position resulting pyrrole five ring target compound. exclusively occupied an –OEt products molybdenum-mediated reaction. The applied similar success alkyne. now-employable significant change composition gives access whole new PTE subfamily, allowing further modulation (physico)-chemical properties such solubility, provides additional insight into formation; it comprises merely partial validation previous hypothesis. alkyne precursors pentathiepines were characterized variety instrumental analyses (NMR, mass spec, UV–vis) six cases (one precursor, unexpected side product, four PTEs) single-crystal X-ray diffraction. Syntheses, isolation procedures, analytical data, impact findings proposed described detail herein.

Language: Английский

Citations

0