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, Год журнала: 2022, Номер 123, С. 105770 - 105770

Опубликована: Апрель 2, 2022

Язык: Английский

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Interactions between gut microbiota and polyphenols: A mechanistic and metabolomic review

Phytomedicine, Год журнала: 2023, Номер 119, С. 154979 - 154979

Опубликована: Июль 18, 2023

Язык: Английский

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An insight into novel therapeutic potentials of taxifolin

Frontiers in Pharmacology, Год журнала: 2023, Номер 14

Опубликована: Май 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.

Язык: 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, Год журнала: 2021, Номер 7(1), С. 875 - 899

Опубликована: Дек. 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.

Язык: 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, Год журнала: 2021, Номер 141, С. 105149 - 105149

Опубликована: Дек. 17, 2021

Язык: 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, Год журнала: 2022, Номер 46(11), С. 5078 - 5090

Опубликована: Янв. 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.

Язык: Английский

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Robust antiviral activity of commonly prescribed antidepressants against emerging coronaviruses: in vitro and in silico drug repurposing studies

Scientific Reports, Год журнала: 2022, Номер 12(1)

Опубликована: Июль 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.

Язык: 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, Год журнала: 2022, Номер 11(3), С. 462 - 462

Опубликована: Фев. 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

Язык: Английский

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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

Journal of Medicinal Chemistry, Год журнала: 2022, Номер 66(1), С. 777 - 792

Опубликована: Дек. 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.

Язык: Английский

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Anticoagulants as Potential SARS-CoV-2 Mpro Inhibitors for COVID-19 Patients: In Vitro, Molecular Docking, Molecular Dynamics, DFT, and SAR Studies

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(20), С. 12235 - 12235

Опубликована: Окт. 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.

Язык: Английский

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