Design, synthesis, and SAR studies of novel 4-methoxyphenyl pyrazole and pyrimidine derivatives as potential dual tyrosine kinase inhibitors targeting both EGFR and VEGFR-2

Bioorganic Chemistry, Journal Year: 2022, Volume and Issue: 123, P. 105770 - 105770

Published: April 2, 2022

Language: Английский

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Inhibition of the main protease of SARS-CoV-2 (Mpro) by repurposing/designing drug-like substances and utilizing nature’s toolbox of bioactive compounds

Computational and Structural Biotechnology Journal, Journal Year: 2022, Volume and Issue: 20, P. 1306 - 1344

Published: Jan. 1, 2022

The emergence of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has resulted in a long pandemic, with numerous cases and victims worldwide enormous consequences on social economic life. Although vaccinations have proceeded provide valuable shield against virus, approved drugs are limited it is crucial that further ways to combat infection developed, can also act potential mutations. main protease (Mpro) virus an appealing target for development inhibitors, due its importance viral life cycle high conservation among different coronaviruses. Several compounds shown inhibitory Mpro, both silico vitro, few them having entered clinical trials. These candidates include: known been repurposed, molecules specifically designed based natural substrate or structural moieties binding affinity active site, as well naturally derived compounds, either isolated plant extracts. aim this work collectively present results research regarding Mpro inhibitors date, focusing function founded by simulations explored vitro vivo assays. Creating extended portfolio promising may block replication inhibiting understanding involved structure-activity relationships, could basis effective solutions SARS-CoV-2 future related outbreaks.

Language: Английский

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Uncovering the Natural Inhibitors From Medicinal Plants to Alleviate Human Cancers Targeting the p53 Protein: An In Silico Approach

ChemistrySelect, Journal Year: 2025, Volume and Issue: 10(1)

Published: Jan. 1, 2025

Abstract The tumor suppressor p53 protein plays a key role in controlling several essential cellular responses, including cell growth, development, and apoptosis, helping to prevent cancer development. In various cancers, loss of function results prolonged replication inhibition programmed death. There are few options available target p53, but they come with limitations. For this reason, there is need for novel drug candidates maintain functionality. Therefore, our study aims identify potential natural bioactive compounds through comprehensive silico methods such as molecular docking, MM/GBSA (molecular mechanics generalized born surface area), ADME/T (absorption, distribution, metabolism, excretion, toxicity), dynamics (MD) simulation against the targeted p53. Initially, 462 phytochemicals from 23 medicinal plants were screened using docking MM‐GBSA studies find phytochemicals. From studies, top three compounds, CID‐3469, CID‐5280372, CID‐591524, selected based on their good binding affinities further investigation, where all showed better drug‐likeness no toxicity analysis. MD depicted structural stability phytocompounds complexes protein. This shows insights into development treatment.

Language: Английский

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Naturally Available Flavonoid Aglycones as Potential Antiviral Drug Candidates against SARS-CoV-2

Molecules, Journal Year: 2021, Volume and Issue: 26(21), P. 6559 - 6559

Published: Oct. 29, 2021

Flavonoids are important secondary plant metabolites that have been studied for a long time their therapeutic potential in inflammatory diseases because of cytokine-modulatory effects. Five flavonoid aglycones were isolated and identified from the hydrolyzed aqueous methanol extracts Anastatica hierochuntica L., Citrus reticulata Blanco, Kickxia aegyptiaca (L.) Nabelek. They as taxifolin (1), pectolinarigenin (2), tangeretin (3), gardenin B (4), hispidulin (5). These structures elucidated based on chromatographic spectral analysis. In this study, molecular docking studies carried out compounds against SARS-CoV-2 main protease (Mpro) compared to co-crystallized inhibitor Mpro (α-ketoamide (KI), IC50 = 66.72 µg/mL) reference standard. Moreover, vitro screening was evaluated. Compounds 2 3 showed highest virus inhibition with 12.4 2.5 µg/mL, respectively. Our findings recommend further advanced vivo examined flavonoids, especially either alone or combination each other identify promising lead target effectively. This is first report activity these SARS-CoV-2.

Language: Английский

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In Silico and In Vitro Studies for Benzimidazole Anthelmintics Repurposing as VEGFR-2 Antagonists: Novel Mebendazole-Loaded Mixed Micelles with Enhanced Dissolution and Anticancer Activity

ACS Omega, Journal Year: 2021, Volume and Issue: 7(1), P. 875 - 899

Published: Dec. 22, 2021

Cancer is a leading cause of death worldwide and its incidence unfortunately anticipated to rise in the next years. On other hand, vascular endothelial growth factor receptor 2 (VEGFR-2) highly expressed tumor-associated cells, where it affects tumor-promoting angiogenesis. Therefore, VEGFR-2 considered one most promising therapeutic targets for cancer treatment. Furthermore, some FDA-approved benzimidazole anthelmintics have already shown potential anticancer activities. repurposing them against can provide rapid effective alternative that be implicated safely Hence, 13 anthelmintic drugs were subjected molecular docking receptor. Among tested compounds, fenbendazole (FBZ, 1), mebendazole (MBZ, 2), albendazole (ABZ, 3) proposed as antagonists. dynamics simulations carried out at 200 ns, giving more information on their thermodynamic dynamic properties. Besides, activity aforementioned was vitro three different cell lines, including liver (HUH7), lung (A549), breast (MCF7) lines. The results depicted cytotoxic especially both HUH7 A549 improve aqueous solubility MBZ, formulated form mixed micelles (MMs) which showed an enhanced drug release with better cytotoxicity compared crude MBZ. Finally, quantification concentration treated cells has been conducted based enzyme-linked immunosorbent assay. disclosed FBZ, ABZ significantly (p < 0.001) reduced VEGFR-2, while lowest inhibition achieved MBZ-loaded MMs, even much than reference sorafenib. Collectively, investigated could encountered lead compounds further structural modifications thus activity, accomplished through studying structure–activity relationships.

Language: Английский

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Methodology-Centered Review of Molecular Modeling, Simulation, and Prediction of SARS-CoV-2

Chemical Reviews, Journal Year: 2022, Volume and Issue: 122(13), P. 11287 - 11368

Published: May 20, 2022

Despite tremendous efforts in the past two years, our understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), virus-host interactions, immune response, virulence, transmission, and evolution is still very limited. This limitation calls for further in-depth investigation. Computational studies have become an indispensable component combating disease 2019 (COVID-19) due to their low cost, efficiency, fact that they are free from safety ethical constraints. Additionally, mechanism governs global transmission SARS-CoV-2 cannot be revealed individual experiments was discovered by integrating genotyping massive viral sequences, biophysical modeling protein-protein deep mutational data, learning, advanced mathematics. There exists a tsunami literature on molecular modeling, simulations, predictions related developments drugs, vaccines, antibodies, diagnostics. To provide readers with quick update about this literature, we present comprehensive systematic methodology-centered review. Aspects such as biophysics, bioinformatics, cheminformatics, machine mathematics discussed. review will beneficial researchers who looking ways contribute those interested status field.

Language: Английский

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In vitro and computational insights revealing the potential inhibitory effect of Tanshinone IIA against influenza A virus

Computers in Biology and Medicine, Journal Year: 2021, Volume and Issue: 141, P. 105149 - 105149

Published: Dec. 17, 2021

Language: Английский

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Newly synthesized series of oxoindole–oxadiazole conjugates as potential anti-SARS-CoV-2 agents:in silicoandin vitrostudies

New Journal of Chemistry, Journal Year: 2022, Volume and Issue: 46(11), P. 5078 - 5090

Published: Jan. 1, 2022

The pharmacophoric features of the novel series 1,3,4-oxadiazole–oxoindole conjugates (IVa–g) as potential anti-SARS-CoV-2 agents based on reported M pro inhibitor (Ia) are presented.

Language: Английский

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Synthesis, structural characterization, DFT calculations, molecular docking, and molecular dynamics simulations of a novel ferrocene derivative to unravel its potential antitumor activity

Journal of Biomolecular Structure and Dynamics, Journal Year: 2022, Volume and Issue: unknown, P. 1 - 18

Published: June 8, 2022

In this article, we describe a set of subsequent five-steps chemical reactions to synthesize ferrocene derivative named 1-(5-(diphenylphosphaneyl)cyclopenta-1,3-dien-1-yl)ethyl)imino)-1,3-dihydroisobenzofuran-5-yl)methanol (compound 10). Structural characterization 10 and its intermediate products was also performed reported attest their formation. A molecular docking study propose the novel synthesized (10) as potential antitumor candidate targeting mitogen-activated protein (MAP) kinases interacting kinase (Mnk) 1. The computed score at -9.50 kcal/mol compared native anticancer staurosporine -8.72 postulated promising activity. Also, dynamics (MD) simulations were carried out for 500 ns followed by MM-GBSA-binding free energy calculations both docked complexes give more deep insights into dynamic behavior in physiological conditions. Furthermore, DFT unravel some physiochemical characteristics (10). quantum mechanics shed light on structural electrochemical configurations which would open horizon further investigation. HighlightsThe synthesis 10) described.Structural characterizations performed.DFT calculations, docking, dynamics, MM-GBSA out.Computational studies revealed through inhibiting 1.Communicated Ramaswamy H. Sarma.

Language: Английский

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Potential Valorization of Edible Nuts By-Products: Exploring the Immune-Modulatory and Antioxidants Effects of Selected Nut Shells Extracts in Relation to Their Metabolic Profiles

Antioxidants, Journal Year: 2022, Volume and Issue: 11(3), P. 462 - 462

Published: Feb. 25, 2022

The immune system is a potent army that defends our body against various infections and diseases through innate adaptive immunity. Herbal medicine one of the essential sources for enhancing immunity because affordability, availability, minor side effects, consumers' preferences. Hazelnuts, walnuts, almonds, peanuts are among most widespread edible nuts rich in phenolics, fats, fibers, vitamins, proteins, minerals. potential nut shells phytoremediation has attracted increasing attention as sustainable solution waste recycling. Here, we determined

Language: Английский

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