Rumex Vesicarius L. extract improves the efficacy of doxorubicin in triple-negative breast cancer through inhibiting Bcl2, mTOR, JNK1 and augmenting p21 expression DOI Creative Commons

Aml Ghanem,

Ahmed A. Al‐Karmalawy, Ahmed I. Abd El Maksoud

et al.

Informatics in Medicine Unlocked, Journal Year: 2022, Volume and Issue: 29, P. 100869 - 100869

Published: Jan. 1, 2022

Doxorubicin (DOX) is a potent chemotherapeutic drug; however, its use limited because it induces dose-dependent oxidative stress causing severe adverse effects. Rumex Vesicarius L. (RMX) plant used in traditional medicine for multiple therapeutic virtues including antioxidant potential. We aimed to determine the potency of RMX alone and combination with DOX against invasive triple-negative breast cancer (TNBC) cell line MDA-MB-231, deduce underlying mechanism action by vitro silico analyses. found that extract significantly inhibited proliferation 50% inhibitory concentration (IC50) 2.12 0.5 μM respectively. Furthermore, combined treatment has induced significant reductions relative gene expression survival/anti-apoptosis invasion genes mTOR, Bcl-2, JNK respectively, while p21 tumor suppressor was increased. In analysis indicated some bioactive compounds exhibit superior affinity inhibit oncogene p21-activated kinase 4 (PAK4), which functions as an inhibitor gene. conclusion, this study reveals enhances anticancer efficacy through molecular mechanisms involving downregulation JNK1, augmenting TNBC possibly targeting PAK4 Finally, we recommend further vivo studies confirm their potential therapy.

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

77
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

71
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

57
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
Synthesis, structural characterization, DFT calculations, molecular docking, and molecular dynamics simulations of a novel ferrocene derivative to unravel its potential antitumor activity DOI

Mohamed M. Hammoud,

Muhammad Khattab,

Marwa Abdel‐Motaal

et al.

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

Citations

52
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

48
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
A Systematic Review of the Global Intervention for SARS-CoV-2 Combating: From Drugs Repurposing to Molnupiravir Approval DOI Creative Commons

Nada A. Ashour,

Ayman Abo Elmaaty,

Amany A. Sarhan

et al.

Drug Design Development and Therapy, Journal Year: 2022, Volume and Issue: Volume 16, P. 685 - 715

Published: March 1, 2022

Abstract: The rising outbreak of SARS-CoV-2 continues to unfold all over the world. development novel effective antiviral drugs fight against is a time cost. As result, some specific FDA-approved have already been repurposed and authorized for COVID-19 treatment. used were either or non-antiviral drugs. Accordingly, present review thoroughly focuses on repurposing efficacy these including clinical trials experienced, combination therapies used, methods followed treatment, their future perspective. Therefore, drug was regarded as an avenue Recently, molnupiravir prodrug medication that approved in United Kingdom November 2021 treatment COVID-19. On other hand, PF-07321332 oral developed by Pfizer. For COVID-19, PF-07321332/ritonavir Phase III studies marketed Paxlovid. Herein, we represented almost history combating from recently available anti-SARS-CoV-2 candidates, new hope end current pandemic. Graphical Keywords: SARS-CoV-2, repurposing, trials, molnupiravir, paxlovid

Language: Английский

Citations

40