Ligand-based design and synthesis of N'-Benzylidene-3,4-dimethoxybenzohydrazide derivatives as potential antimicrobial agents; evaluation by in vitro, in vivo, and in silico approaches with SAR studies DOI Creative Commons

Rogy R. Ezz Eldin,

Marwa A. Saleh, Mohammad Hayal Alotaibi

et al.

Journal of Enzyme Inhibition and Medicinal Chemistry, Journal Year: 2022, Volume and Issue: 37(1), P. 1098 - 1119

Published: April 18, 2022

Herein, a series of N'-benzylidene-3,4-dimethoxybenzohydrazide derivatives were designed and synthesised to target the multidrug efflux pump (MATE). The antibacterial activities screened against S. aureus, Acinetobacter, typhi, E. coli, P. aeruginosa, whereas their antifungal C. albicans. Compounds 4a, 4h, 4i showed most promising activities. Moreover, compounds 4h being broader superior members regarding antimicrobial effects selected be further evaluated via in vivo testing using biochemical analysis liver/kidney histological examination. Additionally, molecular docking was carried out attain deep insights into compounds' binding modes. Also, ADMET studies performed investigate physicochemical/pharmacokinetics features toxicity parameters derivatives. Finally, structure-antimicrobial activity relationship study established facilitate structural modifications future. HighlightsA new targeting (MATE) guided by pharmacophoric co-crystallized native inhibitor protein.The newly assessed through vitro, vivo, silico approaches.Using agar well diffusion assay, whereas, albicans.The minimal inhibitory concentration (MIC) bactericidal (MBC) investigated on variable microbial species.Compounds (4h 4i) -as effects- bio-chemical examination.A performed.A

Language: Английский

Design and synthesis of thiazolidine-2,4-diones hybrids with 1,2-dihydroquinolones and 2-oxindoles as potential VEGFR-2 inhibitors: in-vitro anticancer evaluation and in-silico studies DOI Creative Commons
Mohammed S. Taghour, Hazem Elkady, Wagdy M. Eldehna

et al.

Journal of Enzyme Inhibition and Medicinal Chemistry, Journal Year: 2022, Volume and Issue: 37(1), P. 1903 - 1917

Published: July 8, 2022

A thiazolidine-2,4-dione nucleus was molecularly hybridised with the effective antitumor moieties; 2-oxo-1,2-dihydroquinoline and 2-oxoindoline to obtain new hybrids potential activity against VEGFR-2. The cytotoxic effects of synthesised derivatives Caco-2, HepG-2, MDA-MB-231 cell lines were investigated. Compound 12a found be most potent candidate investigated IC50 values 2, 10, 40 µM, respectively. Furthermore, tested in vitro for their VEGFR-2 inhibitory showing strong inhibition. Moreover, an viability study Vero non-cancerous line results reflected a high safety profile all compounds. further its apoptotic behaviour by assessing gene expression four genes (Bcl2, Bcl-xl, TGF, Survivin). Molecular dynamic simulations authenticated affinity, accurate binding, perfect dynamics compound

Language: Английский

Citations

81
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 DOI
Abeer M. El‐Naggar,

A.M.A. Hassan,

Eslam B. Elkaeed

et al.

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

Published: April 2, 2022

Language: Английский

Citations

75
Synthesis, Molecular Docking, and Dynamic Simulation Targeting Main Protease (Mpro) of New, Thiazole Clubbed Pyridine Scaffolds as Potential COVID-19 Inhibitors DOI Creative Commons
Adel Alghamdi, Amr S. Abouzied, Abdulwahab Alamri

et al.

Current Issues in Molecular Biology, Journal Year: 2023, Volume and Issue: 45(2), P. 1422 - 1442

Published: Feb. 7, 2023

Many biological activities of pyridine and thiazole derivatives have been reported, including antiviral activity and, more recently, as COVID-19 inhibitors. Thus, in this paper, we designed, synthesized, characterized a novel series N-aminothiazole-hydrazineethyl-pyridines, beginning with N'-(1-(pyridine-3-yl)ethylidene)hydrazinecarbothiohydrazide derivative various hydrazonoyl chlorides phenacyl bromides. Their Schiff bases were prepared from the condensation N-aminothiazole 4-methoxybenzaldehyde. FTIR, MS, NMR, elemental studies used to identify new products. The binding energy for non-bonding interactions between ligand (studied compounds) receptor was determined using molecular docking against SARS-CoV-2 main protease (PDB code: 6LU7). Finally, best docked pose highest (8a = -8.6 kcal/mol) selected further dynamics (MD) simulation verify outcomes comprehend thermodynamic properties binding. Through additional vitro vivo research on newly synthesized chemicals, it is envisaged that achieved results will represent significant advancement fight COVID-19.

Language: Английский

Citations

44
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 DOI Creative Commons
Heba A. El Gizawy, Sylvia A. Boshra,

Ahmed Mostafa

et al.

Molecules, Journal Year: 2021, Volume and Issue: 26(19), P. 5844 - 5844

Published: Sept. 27, 2021

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

Language: Английский

Citations

74
Investigating the structure–activity relationship of marine natural polyketides as promising SARS-CoV-2 main protease inhibitors DOI Creative Commons
Amr El‐Demerdash, Ahmed A. Al‐Karmalawy, Tarek Mohamed Abd El‐Aziz

et al.

RSC Advances, Journal Year: 2021, Volume and Issue: 11(50), P. 31339 - 31363

Published: Jan. 1, 2021

Since its first report in December 2019, the novel coronavirus virus, SARS-CoV-2, has caused an unprecedented global health crisis and economic loss imposing a tremendous burden on worldwide finance, healthcare system, even daily life. Even with introduction of different preventive vaccines, there is still dire need for effective antiviral therapeutics. Nature been considered as historical trove drug discovery development, particularly cases crises. Herein, comprehensive

Language: Английский

Citations

70
Naturally Available Flavonoid Aglycones as Potential Antiviral Drug Candidates against SARS-CoV-2 DOI Creative Commons
Ahmed A. Al‐Karmalawy, Mai M. Farid,

Ahmed Mostafa

et al.

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

Citations

70
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 DOI Creative Commons
Ayman Abo Elmaaty, Khaled M. Darwish, Amani Chrouda

et al.

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

Citations

69
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 DOI Creative Commons
Maha M. Abdel‐Fattah, Khaled M. Darwish, Raya Soltane

et al.

RSC Advances, Journal Year: 2021, Volume and Issue: 11(56), P. 35536 - 35558

Published: Jan. 1, 2021

Hydroxyethylamine and hydroxyethylene moieties of β-blockers exert potential SARS-CoV-2 inhibitory effects: rational-based design in silico , vitro SAR Studies.

Language: Английский

Citations

56
In vitro and computational insights revealing the potential inhibitory effect of Tanshinone IIA against influenza A virus DOI
Dalia Elebeedy,

Ingy Badawy,

Ayman Abo Elmaaty

et al.

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

Published: Dec. 17, 2021

Language: Английский

Citations

56
Newly synthesized series of oxoindole–oxadiazole conjugates as potential anti-SARS-CoV-2 agents:in silicoandin vitrostudies DOI

Rana M. El-Masry,

Ahmed A. Al‐Karmalawy, Radwan Alnajjar

et al.

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

Citations

55