Data-driven dentistry: Computational revelations redefining pulp capping DOI Creative Commons
N. Kiran Kumar,

V. Swetha Geervani,

Rupesh Kumar

et al.

Journal of Conservative Dentistry and Endodontics, Journal Year: 2024, Volume and Issue: 27(6), P. 649 - 653

Published: June 1, 2024

Abstract Introduction: Pulpal and periradicular diseases stem from immune reactions to microbiota, causing inflammation. Limited blood supply hampers dental pulp self-healing. Managing inflammation involves eliminating bacteria reducing pro-inflammatory mediators especially MMP-9, which has a significant correlation with pulpitis. s. Flavonoids like Hesperidin, Baicalein, Epigallocatechin gallate, Genistein, Icariin, Quercetin show potential for capping. Aim: This in-silico study compares various their anti-inflammatory effects on Chlorhexidine as control, known MMP-9 inhibitor. Materials Methods: Protein Ligand Preparation: The human catalytic domain (PDB ID: 4XCT) structure was retrieved, necessary modifications were made. PubChem database prepared docking using AutoDock Vina. A grid created, molecular dynamics simulations conducted Gromacs-2019.4 GROMOS96 force field. Trajectory analysis performed, MM-PBSA calculation determined binding free energies. Results: Analysis of ligand interactions revealed Hesperidin’s high affinity, forming numerous hydrogen bonds specific amino acids. Molecular confirmed stability, RMSD, RMSF, Rg, SASA indicating consistent complex behaviour over 100 ns. affirmed favourable energy contributions in MMP-9-Hesperidin interactions. Conclusion: plays crucial role prognosis Incorporating inhibitors into capping agents may enhance therapeutic efficacy. Hesperidin emerges potent inhibitor, warranting further vivo validation against other agents.

Language: Английский

ADME profiling, molecular docking, DFT, and MEP analysis reveal cissamaline, cissamanine, and cissamdine from Cissampelos capensis L.f. as potential anti-Alzheimer's agents DOI Creative Commons
Maram B. Alhawarri,

Mohammad G. Al‐Thiabat,

Amit Dubey

et al.

RSC Advances, Journal Year: 2024, Volume and Issue: 14(14), P. 9878 - 9891

Published: Jan. 1, 2024

Proaporphine alkaloids—cissamaline, cissamanine, and cissamdine—show promise against AD, with in silico studies highlighting their potential as new therapeutics.

Language: Английский

Citations

21
Icariin prevents methylmercury-induced experimental neurotoxicity: Evidence from cerebrospinal fluid, blood plasma, brain samples, and in-silico investigations DOI Creative Commons

Sarthak Sharma,

Sidharth Mehan, Zuber Khan

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 10(1), P. e24050 - e24050

Published: Jan. 1, 2024

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease that causes significant neurodegeneration. Methylmercury (MeHg) neurotoxin induces axonal neurodegeneration and motor nerve degeneration by destroying oligodendrocytes, degenerating white matter, inducing apoptosis, excitotoxicity, reducing myelin basic protein (MBP). This study examines the inhibition of SIRT-1 (silence information regulator 1), Nrf-2 (nuclear factor E2-related 2), HO-1 (heme oxygenase TDP-43 (TAR-DNA-binding 43) accumulation in context ALS, as well modulation these proteins icariin (15 30 mg/kg, orally), glycoside flavonoid with neuroprotective properties. Neuroprotective activates SIRT-1, Nrf-2, HO-1, mitigating inflammation neuronal injury disorders. In-vivo in-silico testing experimental ALS models confirmed efficacy modulating cellular targets. The addition sirtinol 10 an inhibitor helps determine effectiveness icariin. In this study, we also examined neurobehavioral, neurochemical, histopathological, LFB (Luxol fast blue) markers various biological samples, including Cerebrospinal fluid (CSF), blood plasma, brain homogenates (Cerebral Cortex, Hippocampus, Striatum, mid-brain, Cerebellum). These results demonstrate administration ameliorates mechanism underlying benefits likely related to regulating signaling pathways.

Language: Английский

Citations

9
Enhancing the Therapeutic Effect in Alzheimer's Disease Drugs: The role of Polypharmacology and Cholinesterase inhibitors DOI Creative Commons
M. Margarida Martins, Paula S. Branco, Luı́sa M. Ferreira

et al.

ChemistrySelect, Journal Year: 2023, Volume and Issue: 8(10)

Published: March 7, 2023

Abstract Alzheimer's disease (AD) is a devastating syndrome that accounts for 60–70 % of all dementia cases, putting an enormous burden on global healthcare and economy. Unfortunately, there no cure AD, the currently approved drugs are limited in their effects. Given various pathological mechanisms behind “one‐target, one‐drug” paradigm drug design became obsolete, new paradigm, polypharmacology, emerged. Consequently, greater focus has been put towards multi‐target directed ligands (MTDLs), as these can regulate several targets operating network. Parallel to that, cholinesterase inhibitors have regained popularity after decades being considered only symptomatic agents with disease‐modifying properties. In this review, current AD hypotheses therapeutic targets, concept polypharmacology pathology importance cholinesterases pathogenesis biochemical processes discussed, final overview development cholinesterase‐based MTDLs.

Language: Английский

Citations

18
Advances of computer-aided drug design (CADD) in the development of anti-Azheimer’s-disease drugs DOI
Yuzhen Niu, Ping Lin

Drug Discovery Today, Journal Year: 2023, Volume and Issue: 28(8), P. 103665 - 103665

Published: June 10, 2023

Language: Английский

Citations

15
Adsorption of toremifene on carboxylic acid functionalized N/B-doped coronene: DFT, AIM, solvation, docking and MD analyses DOI
Jamelah S. Al‐Otaibi, Y. Sheena Mary, Y. Sheena Mary

et al.

Journal of Molecular Liquids, Journal Year: 2024, Volume and Issue: 395, P. 123931 - 123931

Published: Jan. 2, 2024

Language: Английский

Citations

5
Regenerative marine waste towards CaCO3 nanoformulation for Alzheimer's therapy DOI

Prakashkumar Nallasamy,

Rajamohamed Beema Shafreen,

Jeyakanthan Jeyaraman

et al.

Environmental Research, Journal Year: 2023, Volume and Issue: 225, P. 115631 - 115631

Published: March 7, 2023

Language: Английский

Citations

11
Contilisant+Tubastatin A Hybrids: Polyfunctionalized Indole Derivatives as New HDAC Inhibitor-Based Multitarget Small Molecules with In Vitro and In Vivo Activity in Neurodegenerative Diseases DOI
Mireia Toledano‐Pinedo,

Alicia Porro-Pérez,

Linda Schäker‐Hübner

et al.

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 10, 2024

Herein, we describe the design, synthesis, and biological evaluation of 15

Language: Английский

Citations

4
A Survey on Computational Methods in Drug Discovery for Neurodegenerative Diseases DOI Creative Commons

Caterina Vicidomini,

Francesco Fontanella, Tiziana D’Alessandro

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(10), P. 1330 - 1330

Published: Oct. 19, 2024

Currently, the age structure of world population is changing due to declining birth rates and increasing life expectancy. As a result, physicians worldwide have treat an number age-related diseases, which neurological disorders represent significant part. In this context, there urgent need discover new therapeutic approaches counteract effects neurodegeneration on human health, computational science can be pivotal importance for more effective neurodrug discovery. The knowledge molecular receptors other biomolecules involved in pathogenesis facilitates design molecules as potential drugs used fight against diseases high social relevance such dementia, Alzheimer's disease (AD) Parkinson's (PD), cite only few. However, absence comprehensive guidelines regarding strengths weaknesses alternative creates fragmented disconnected field, resulting missed opportunities enhance performance achieve successful applications. This review aims summarize some most innovative strategies based methods development. particular, recent applications state-of-the-art docking artificial intelligence ligand- target-based novel drug were reviewed, highlighting crucial role silico context discovery neurodegenerative diseases.

Language: Английский

Citations

4
Analysis of total RNA as a potential biomarker of Parkinson’s disease in silico DOI Creative Commons
Snežana M Jovičić

International Journal of Immunopathology and Pharmacology, Journal Year: 2025, Volume and Issue: 39

Published: Jan. 1, 2025

Knowledge about total RNA molecules in Parkinson’s disease is limited. This gene expression profiling study was conducted with a preclinical experimental design using mouse model to examine the molecular-biological characteristics and pathological implication of interaction silico. In silico analysis molecules, Gene Expression Omnibus database, published results, preliminary findings available patient samples apply. The potential signaling network effect predicted confirmed. research consists four parts. At first, we analyzed control MPTP groups. second part, FVB-N MPTP. third controls. fourth MTPT separately. constructed contains RNA, where Kyoto Encyclopedia Genes Genomes database showed that genes from pathway are involved development complications male female rats. Identified altered signaling. There direct interconnection interdependence interactions network. Results identified significant total-RNA connect other molecules. shows upregulated downregulated Preliminary data interact genes, they applicable course monitoring, shedding light on how factors impact offering strategies for management.

Language: Английский

Citations

0
Therapeutic exploration potential of adenosine receptor antagonists through pharmacophore ligand-based modelling and pharmacokinetics studies against Parkinson disease DOI
Abduljelil Ajala,

Otaru Habiba Asipita,

Abatyough Terungwa Michael

et al.

In Silico Pharmacology, Journal Year: 2025, Volume and Issue: 13(1)

Published: Jan. 25, 2025

Language: Английский

Citations

0