Design and statistical optimisation of emulsomal nanoparticles for improved anti-SARS-CoV-2 activity of N -(5-nitrothiazol-2-yl)-carboxamido candidates: in vitro and in silico studies DOI Creative Commons
Ahmed A. Al‐Karmalawy, Dalia S. El‐Gamil, Rabeh El‐Shesheny

et al.

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

Published: April 24, 2023

In this article, emulsomes (EMLs) were fabricated to encapsulate the N-(5-nitrothiazol-2-yl)-carboxamido derivatives (3a-3g) in an attempt improve their biological availability and antiviral activity. Next, both cytotoxicity anti-SARS-CoV-2 activities of examined compounds loaded EMLs (F3a-g) assessed Vero E6 cells via MTT assay calculate CC50 inhibitory concentration 50 (IC50) values. The most potent 3e-loaded (F3e) elicited a selectivity index 18 with IC50 value 0.73 μg/mL. Moreover, F3e was selected for further elucidation possible mode action where results showed that it exhibited combination virucidal (>90%), viral adsorption (>80%), replication (>60%) inhibition. Besides, molecular docking MD simulations towards SARS-CoV-2 Mpro performed. Finally, structure-activity relationship (SAR) study focussed on studying influence altering size, type, flexibility α-substituent carboxamide addition compound contraction activity.HighlightsEmulsomes (3a-3g).The μg/mL against SARS-CoV-2.F3e inhibition.Molecular docking, dynamics (MD) simulations, MM-GBSA calculations performed.Structure-activity discussed

Language: Английский

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
Interactions between gut microbiota and polyphenols: A mechanistic and metabolomic review DOI
Hao Cheng, Dandan Zhang, Jing Wu

et al.

Phytomedicine, Journal Year: 2023, Volume and Issue: 119, P. 154979 - 154979

Published: July 18, 2023

Language: Английский

Citations

63
An insight into novel therapeutic potentials of taxifolin DOI Creative Commons
Yang Liu, Xiaolu Shi,

Ye Tian

et al.

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: May 12, 2023

Taxifolin is a flavonoid compound, originally isolated from the bark of Douglas fir trees, which often found in foods such as onions and olive oil, also used commercial preparations, has attracted interest nutritionists medicinal chemists due to its broad range health-promoting effects. It powerful antioxidant with excellent antioxidant, anti-inflammatory, anti-microbial other pharmacological activities. This review focuses on breakthroughs taxifolin for treatment diseases 2019 2022 according various systems human body, nervous system, immune digestive basis this review, we summarize problems current research try suggest solutions future directions.

Language: Английский

Citations

46
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
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
Robust antiviral activity of commonly prescribed antidepressants against emerging coronaviruses: in vitro and in silico drug repurposing studies DOI Creative Commons
Omnia Kutkat, Yassmin Moatasim, Ahmed A. Al‐Karmalawy

et al.

Scientific Reports, Journal Year: 2022, Volume and Issue: 12(1)

Published: July 28, 2022

Abstract During the current coronavirus disease 2019 (COVID-19) pandemic, symptoms of depression are commonly documented among both symptomatic and asymptomatic quarantined COVID-19 patients. Despite that many FDA-approved drugs have been showed anti-SARS-CoV-2 activity in vitro remarkable efficacy against clinical trials, no pharmaceutical products yet declared to be fully effective for treating COVID-19. Antidepressants comprise five major drug classes treatment depression, neuralgia, migraine prophylaxis, eating disorders which frequently reported Herein, eight prescribed antidepressants on inhibition SARS-CoV-2 MERS-CoV was assessed. Additionally, anti-MERS-CoV activities were evaluated. Furthermore, molecular docking studies performed these spike (S) main protease (M pro ) pockets MERS-CoV. Results Amitriptyline, Imipramine, Paroxetine, Sertraline had potential anti-viral activities. Our findings suggested aforementioned deserve more vivo targeting especially those patients suffering from depression.

Language: Английский

Citations

48
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 DOI Creative Commons
Mohamed A. Salem, Nora M. Aborehab, Ahmed A. Al‐Karmalawy

et al.

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

Citations

46
Ligand-Based Design on the Dog-Bone-Shaped BIBR1532 Pharmacophoric Features and Synthesis of Novel Analogues as Promising Telomerase Inhibitors with In Vitro and In Vivo Evaluations DOI
Ahmed A. Al‐Karmalawy, Mohamed S. Nafie, Moataz A. Shaldam

et al.

Journal of Medicinal Chemistry, Journal Year: 2022, Volume and Issue: 66(1), P. 777 - 792

Published: Dec. 16, 2022

Telomerase is an outstanding biological target for cancer treatment. BIBR1532 a non-nucleoside selective telomerase inhibitor; however, it experiences ineligible pharmacokinetics. Herein, we aimed to design new BIBR1532-based analogues as promising inhibitors. Therefore, two novel series of pyridazine-linked cyclopenta[b]thiophene (8a-f) and tetrahydro-1-benzothiophene (9a-f) were synthesized. A quantitative real-time polymerase chain reaction was utilized investigate the inhibitory activity candidates. Notably, 8e 9e exhibited best inhibition profiles. Moreover, showed strong antitumor effects against both MCF-7 A549 cell lines. The on cycle apoptosis measured. Besides, evaluated its in vivo using solid Ehrlich carcinoma. reduction tumor weight volume greater than doxorubicin. Also, molecular docking ADME studies performed. Finally, SAR study conducted gain further insights into different potentials upon variable structural modifications.

Language: Английский

Citations

43
Anticoagulants as Potential SARS-CoV-2 Mpro Inhibitors for COVID-19 Patients: In Vitro, Molecular Docking, Molecular Dynamics, DFT, and SAR Studies DOI Open Access
Ayman Abo Elmaaty, Wagdy M. Eldehna, Muhammad Khattab

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(20), P. 12235 - 12235

Published: Oct. 13, 2022

In this article, 34 anticoagulant drugs were screened in silico against the main protease (Mpro) of SARS-CoV-2 using molecular docking tools. Idraparinux, fondaparinux, eptifibatide, heparin, and ticagrelor demonstrated highest binding affinities towards Mpro. A dynamics study at 200 ns was also carried out for most promising anticoagulants to provide insights into dynamic thermodynamic properties compounds. Moreover, a quantum mechanical conducted which helped us attest some findings. biological evaluation (in vitro) compounds performed by carrying MTT cytotoxicity assay crystal violet order assess inhibitory concentration 50 (IC50). It is worth noting that displayed intrinsic potential inhibition with an IC50 value 5.60 µM safety index 25.33. addition, fondaparinux sodium dabigatran showed activities values 8.60 9.40 µM, respectively, indexes 17.60 15.10, respectively. Mpro enzyme investigated utilizing tipranavir as reference standard. Interestingly, attained 2.36 surpassing (IC50 = 7.38 µM) more than three-fold. Furthermore, highly eligible 10.59 µM. Finally, SAR discussed, counting on findings both vitro approaches.

Language: Английский

Citations

42