UHPLC and Computational Studies of Chemical Constituents Derived from Myrica esculenta against NADPH Oxidase 2 (NOX2) Protein

ChemistrySelect, Journal Year: 2025, Volume and Issue: 10(14)

Published: April 1, 2025

Abstract Here, we employed a combination of UHPLC and in silico approaches to evaluate the inhibitory effects compounds from Myrica esculenta (M. esculenta) plant on NOX2 protein. Compounds methanol extract this were examined using technique. Pharmacophore ADMET studies used Ligandscout 4.4.5 Swiss ADME tools respectively. Molecular docking, MD simulation (triplicate), MMGBSA computation performed Schrödinger 2021–2 software. The method demonstrated that M. contained six compounds: rutin, chlorogenic acid, fisetin, quercetin, myricetin, fumaric acid. modelling results revealed all show significant number interacting functionalities their pharmacophores, suggested they would be excellent drug leads for oral administration. In molecular docking studies, rutin had highest score −9.82 compared reference compound ascorbic which −7.80 score. data indicated was significantly stable within binding pocket NOX2, exploring tightly attachment throughout simulation. Furthermore, complex's Gibbs free energy estimated analysis, validated its stability. We believe our research has potential assist scientific community developing inhibitors management ROS‐mediated diseases, with further use vitro vivo testing.

Language: Английский

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Development of gold nanoparticle-based biosensors for COVID-19 diagnosis

Beni-Suef University Journal of Basic and Applied Sciences, Journal Year: 2022, Volume and Issue: 11(1)

Published: Sept. 5, 2022

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative organism of disease 2019 (COVID-19) which poses a significant threat to public health worldwide. Though there are certain recommended drugs that can cure COVID-19, their therapeutic efficacy limited. Therefore, early and rapid detection without compromising test accuracy necessary in order provide an appropriate treatment for suppression. Main body Nanoparticles (NPs) closely mimic virus interact strongly with its proteins due morphological similarities. NPs have been widely applied variety medical applications, including biosensing, drug delivery, antimicrobial treatment, imaging. Recently, NPs-based biosensors attracted great interest biological activities specific sensing properties, allows analytes such as nucleic acids (DNA or RNA), aptamers, clinical samples. Further, advances nanotechnologies enabled development miniaturized systems point-of-care biosensors, new strategy detecting human viral diseases. Among various NPs, physicochemical properties gold (AuNPs) being used field diagnostics. As result, several AuNP-based colorimetric methods developed. Short conclusion The purpose this review overview AuNPs-based by virtue powerful characteristics signal amplifier enhancer target pathogenic RNA viruses reliable effective existing newly emerging SARS-CoV-2.

Language: Английский

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Targeting the omicron variant of SARS-CoV-2 with phytochemicals from Saudi medicinal plants: molecular docking combined with molecular dynamics investigations

Journal of Biomolecular Structure and Dynamics, Journal Year: 2022, Volume and Issue: 41(19), P. 9732 - 9744

Published: Nov. 11, 2022

The new health crises caused by SARS-CoV-2 have resulted in millions of deaths worldwide. First discovered November 2021, the omicron variant is more transmissible and able to evade immune system better than other previously identified variants, leading a spike cases. Great efforts been made discover inhibitors against SARS-CoV-2. Main protease (Mpro) are considered promising anti-SARS-CoV-2 agents. U.S. FDA has issued an Emergency Use Authorization for ritonavir-boosted nirmatrelvir. Nirmatrelvir first orally bioavailable inhibitor Mpro. There urgent need monitor mutations solve problem resistance, especially Mpro, which contains one mutation - P132H. In present study, 132,57 phytochemicals from 80 medicinal plants grown Saudi Arabia were docked into active site Mpro variant. Free binding energies also calculated. This led discovery five that showed docking scores bound ligand addition, these molecules exhibited favorable free energies. stability compounds 1-5 with protein was studied using molecular dynamics (MD) simulations. These acceptable ADMET properties. results compared wild type. candidates could be envisioned as hits SARS-CoV-2.Communicated Ramaswamy H. Sarma.

Language: Английский

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Analgesic and Anti-Inflammatory Potential of Indole Derivatives

Polycyclic aromatic compounds, Journal Year: 2022, Volume and Issue: 43(9), P. 7732 - 7753

Published: Nov. 10, 2022

Some indole analogues show a good analgesic activity but on the other hand, it has some serious side effects like gastric ulcer. Therefore, there is still need to develop derivatives of non-steroidal anti-inflammatory drugs (NSAIDs) with fewer effects. For this purpose, were prepared objectives new maximum efficacy and minimum 1-(1H-indol-1-yl)-2-(sübstituephenoxy)-ethan-1-one (M1–M4) analyzed further by thin-layer chromatorgarphy (TLC), melting point, IR, 1H-NMR. The synthesized compounds then underwent oral toxicity studies that include hematological, biochemical, histopathological findings. compound was evaluated for in vivo activities carrageenan-induced rat paw edema acetic acid-induced writhing methods. As result biological activities, promising results obtained M2 (2-(2-aminophenoxy)-1-(1H-indol-1-yl)ethanone) subjected studies. It found practically nontoxic, no clinical abnormalities hematology biochemistry, correlated observation. also showed significant at its high dose (400 mg/kg). study suggested have activities. possible mechanism might suggest being act as central anti-nociceptive agent peripheral inhibitor painful inflammation. action whose explained molecular docking against COX-1 COX-2, most active formed −9.3 −8.3 binding energies COX-2. In addition, dynamics (MD) simulation both M2’s complexes COX-2 performed examine stability behavior pose, MM-PBSA free measured −153.820 ± 11.782 −172.604 9.591, respectively. Based computational ADME studies, comply limiting guidelines.

Language: Английский

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Resveratrol and Its Natural Analogues Inhibit RNA Dependant RNA Polymerase (RdRp) of Rhizopus oryzae in Mucormycosis through Computational Investigations

Polycyclic aromatic compounds, Journal Year: 2022, Volume and Issue: 43(5), P. 4426 - 4443

Published: June 27, 2022

Mucormycosis (or black fungus infection) is a life-threatening, but rare fungal infection with predominant occurrence in immunosuppressed patients following the SARS-CoV-2 infection. Rhizopus oryzae (R. O.) causes about 70% of all cases mucormycosis. RNA dependent polymerase (RdRp) key protein implicated genome replication and multiplication R. oryzae. In view biological significance resveratrol (RES), rich grape skin extract, on various microbial infections inflammatory diseases including gum periodontitis, our present study was aimed at silico investigation RES its two natural analogues, piceatannol (3,5,3',4'-tetrahydroxy-trans-stilbene, PIC), 3,5,4'-trimethoxy-trans-stilbene (TMS) for their development as successful antifungal agents targeting O. specific RdRp to combat deadly Due unavailability three-dimensional structure Protein Database Bank (PDB), modeled using target sequence RT/Duplex (Set-Met) (PDB ID: 6AR3, 3.41 Å) by homology modeling. Using RdRp, docking molecular dynamics (MD) simulation studies were carried out Schrödinger suite version 2021-2 software. The findings docking, MD simulations MM-PBSA binding energies conclude that RES, PIC TMS possess predictable stable affinity/interactions RdRp. These bioactive compounds could potentially inhibit activity Further, density function theory (DFT) analysis (B3LYP, 6-311 G* basis set) performed, results DFT indicate compound be more potential inhibitor over RES. drug-likeness ADMET prediction studies, exhibited acceptable drug-likeness, Lipinski's rule five pharmacokinetic parameters. Finally, it can concluded are inhibitors based studies.

Language: Английский

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Coagulopathy and thromboembolic events a pathogenic mechanism of COVID‐19 associated with mortality: An updated review

Journal of Clinical Laboratory Analysis, Journal Year: 2023, Volume and Issue: 37(11-12)

Published: June 1, 2023

During 2019, the SARS-CoV-2 emerged from China, and during months, COVID-19 spread in many countries around world. The expanding data about pathogenesis of this virus could elucidate exact mechanism by which caused death humans. One pathogenic mechanisms disease is coagulation. Coagulation disorders that affect both venous arterial systems occur patients with COVID-19. possible involved coagulation be excessive inflammation induced SARS-CoV-2. However, it not yet clear well how promotes coagulopathy. some factors, such as pulmonary endothelial cell damage anticoagulant system disorders, are assumed to have an important role. In study, we assessed conducted studies COVID-19-induced coagulopathy obtain clearer vision wide range manifestations mechanisms.

Language: Английский

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Drug repurposing against fucosyltransferase-2 via docking, STD-NMR, and molecular dynamic simulation studies

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(11), P. e0308517 - e0308517

Published: Nov. 1, 2024

Aberrant fucosylation is the hallmark of malignant cell transformation, leading to many cellular events, such as uncontrolled proliferation, angiogenesis, tumor invasion, and metastasis. This increased caused due over-expression fucosyltransferases (FUTs) that catalyzes transfer fucose (Fuc) residue from GDP-fucose (donor substrate) various oligosaccharides, glycoproteins, glycolipids (acceptor substrates). Hence, are considered validated target for drug discovery against on cancers. In current study, a repurposing approach was deployed identify new hits fucosyltransferase 2 (FUT2), using computational biophysical techniques. A library 500 US-FDA approved drugs were screened in-silico (FUT2) donor acceptor sites. Five predicted hits, based their significant docking scores (-5.8 -8.2), binding energies (-43 -51.19 Kcal/mol). Furthermore, STD-NMR highlighted epitope these in site (FUT2). Simulation studies provided insights about drugs, 4 them, acarbose, ascorbic acid, ibuprofen, enalaprilat dihydrate, found binders at study reports repurposed potential These may be further studied through in-vitro in-vivo inhibitory mechanistic studies.

Language: Английский

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The hope and hype of ellagic acid and urolithins as ligands of SARS-CoV-2 Nsp5 and inhibitors of viral replication

Journal of Enzyme Inhibition and Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 38(1)

Published: Aug. 28, 2023

Non-structural protein 5 (Nsp5) is a cysteine protease that plays key role in SARS-CoV-2 replication, suppressing host synthesis and promoting immune evasion. The investigation of natural products as potential strategy for Nsp5 inhibition gaining attention means developing antiviral agents. In this work, we have investigated the physicochemical properties structure-activity relationships ellagic acid its gut metabolites, urolithins A-D, ligands Nsp5. Results allow us to identify urolithin D promising ligand Nsp5, with dissociation constant nanomolar range potency. Although able bind catalytic cleft appraisal viral replication against Vero E6 assay highlights lack activity. While these results are discussed framework available literature reporting conflicting data on polyphenol activity, they provide new clues inhibitors.

Language: Английский

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Design, docking, MD simulation and in-silco ADMET prediction studies of novel indole-based benzamides targeting estrogen receptor alfa positive for effective breast cancer therapy

Pharmacia, Journal Year: 2023, Volume and Issue: 70(2), P. 307 - 316

Published: May 11, 2023

Breast cancer is one of the most common malignancies in women, afflicting millions lives each year. Our current study suggests that development promising 7-substituted -1-(4-(piperidine-1-yl methoxy)benzyl)-1H-indole-3-carboxamide derivatives results potent anticancer agents through in-silico investigations. The molecular docking was performed against estrogen receptor alpha (ER-α) positive (PDB ID: 3UUD) breast cells to anticipate binding modes designed compounds and likely mode action. interactions between ligands amino acid residues were thoroughly elucidated. stability docked protein-ligand complexes further confirmed by 100 ns simulations methods. From studies, indole-based benzamides exhibited satisfactory physicochemical, drug-likeness toxicity properties. To conclude, substituted benzamide analogs on indole ring could serve as a possible modulator ER-α cancer.

Language: Английский

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A beginner’s guide to molecular docking

Sciences of Phytochemistry, Journal Year: 2022, Volume and Issue: 1(2), P. 37 - 40

Published: Dec. 2, 2022

In this opinion, the basics of molecular docking (MD) such as binding affinity, pose, and ligand interactions with common docking-related terminologies (Apo protein, positive control, native ligand, co-crystal inhibitors) are discussed. We have provided different figures to aid in graphical interpretation discussed literature. Following this, a few advantages (simplicity, fast, applicability) disadvantages MD highlighted. This opinion will benefit bachelor master students (or anyone) that interested learning technique MD. encourage sensible use strict analysis avoid errors results. The should be collectively considered during result analysis. For every study, we strongly recommend validation protocols.

Language: Английский

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