Design and synthesis of new 4-(2-nitrophenoxy)benzamide derivatives as potential antiviral agents: molecular modeling and <i>in vitro</i> antiviral screening

Abdallah, Abdallah E.; Alesawy, Mohamed S; Eissa, Sally I.; El‐Fakharany, Esmail M.; Kalaba, Mohamed H.; Sharaf, Mohamed H.; Shama, Noura M. Abo; Mahmoud, Sara H.; Mostafa, Ahmed; Al‐Karmalawy, Ahmed A.; Elkady, Hazem

doi:10.1039/d1nj02710g

Cited by 54 publications

(33 citation statements)

References 62 publications

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“…The 2D chemical structures of the isolated five flavonoids-taxifolin (1), pectolinarigenin (2), tangeretin (3), gardenin B (4), and hispidulin (5)-were sketched using Chem-Draw Professional. Each chemical structure was introduced separately into the MOE window, converted to the 3D orientation, adjusted for partial charges, and energy minimized to be prepared for docking according to the default preparation steps described earlier [53][54][55][56]. After saving each prepared compound separately using the (.moe) extension, the co-crystallized native inhibitor of SARS-CoV-2 Mpro (KI) was extracted and saved in a separate MOE file as well.…”

Section: Preparation Of the Isolated And Identified Five Flavonoids (1-5)mentioning

confidence: 99%

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

et al. 2021

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

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Section: Preparation Of the Isolated And Identified Five Flavonoids (1-5)mentioning

confidence: 99%

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

et al. 2021

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“…The best pose for each ligand with the most acceptable score, binding mode, and RMSD value was selected for further studies. It is worth clarifying that a program validation step was performed first for the applied MOE program by redocking the co-crystallized native inhibitor (N3) at its binding pocket of the prepared main protease [78,79]. A valid performance was confirmed by obtaining a low RMSD value (1.43) between the native and redocked N3 ligands (Figure 10).…”

Section: The Target Mpro Of Sars-cov-2 Preparationmentioning

confidence: 99%

Pimenta dioica (L.) Merr. Bioactive Constituents Exert Anti-SARS-CoV-2 and Anti-Inflammatory Activities: Molecular Docking and Dynamics, In Vitro, and In Vivo Studies

et al. 2021

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In response to the urgent need to control Coronavirus disease 19 (COVID-19), this study aims to explore potential anti-SARS-CoV-2 agents from natural sources. Moreover, cytokine immunological responses to the viral infection could lead to acute respiratory distress which is considered a critical and life-threatening complication associated with the infection. Therefore, the anti-viral and anti-inflammatory agents can be key to the management of patients with COVID-19. Four bioactive compounds, namely ferulic acid 1, rutin 2, gallic acid 3, and chlorogenic acid 4 were isolated from the leaves of Pimenta dioica (L.) Merr (ethyl acetate extract) and identified using spectroscopic evidence. Furthermore, molecular docking and dynamics simulations were performed for the isolated and identified compounds (1–4) against SARS-CoV-2 main protease (Mpro) as a proposed mechanism of action. Furthermore, all compounds were tested for their half-maximal cytotoxicity (CC50) and SARS-CoV-2 inhibitory concentrations (IC50). Additionally, lung toxicity was induced in rats by mercuric chloride and the effects of treatment with P. dioca aqueous extract, ferulic acid 1, rutin 2, gallic acid 3, and chlorogenic acid 4 were recorded through measuring TNF-α, IL-1β, IL-2, IL-10, G-CSF, and genetic expression of miRNA 21-3P and miRNA-155 levels to assess their anti-inflammatory effects essential for COVID-19 patients. Interestingly, rutin 2, gallic acid 3, and chlorogenic acid 4 showed remarkable anti-SARS-CoV-2 activities with IC50 values of 31 µg/mL, 108 μg/mL, and 360 µg/mL, respectively. Moreover, the anti-inflammatory effects were found to be better in ferulic acid 1 and rutin 2 treatments. Our results could be promising for more advanced preclinical and clinical studies especially on rutin 2 either alone or in combination with other isolates for COVID-19 management.

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“…The tested compounds together with the cocrystallized ligand (N3) were imported in the same database and saved in the form of MDB le for the docking calculations with target protease as described earlier. 35,36…”

Section: Preparation Of the Tested B-adrenergic Blockersmentioning

confidence: 99%

β-Blockers bearing hydroxyethylamine and hydroxyethylene as potential SARS-CoV-2 Mpro inhibitors: rational based design,in silico,in vitro, and SAR studies for lead optimization

et al. 2021

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Design and synthesis of new 4-(2-nitrophenoxy)benzamide derivatives as potential antiviral agents: molecular modeling and in vitro antiviral screening

Abstract: Novel benzamide derivatives as anti adenovirus, HSV-1, coxsackievirus, and SARS-CoV-2: in vitro and in silico study.

Cited by 54 publications

References 62 publications

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

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

Pimenta dioica (L.) Merr. Bioactive Constituents Exert Anti-SARS-CoV-2 and Anti-Inflammatory Activities: Molecular Docking and Dynamics, In Vitro, and In Vivo Studies

β-Blockers bearing hydroxyethylamine and hydroxyethylene as potential SARS-CoV-2 Mpro inhibitors: rational based design,in silico,in vitro, and SAR studies for lead optimization

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