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واجهت الدولة العباسية العديد من الازمات الاقتصادية والمالية التي جاءت لأسباب عدة، يعود بعضها إلى التغيرات التي تحدث في النفقات العامة، وبعضها الاخر يتعلق بالتغيرات التي تحدث في الإيرادات العامة للدولة، وبمعنى آخر، فإن العامل الأول لحدوث عجز الموازنة العامة يتمثل في تزايد معدلات نمو النفقات العامة من ناحية، لأسباب متنوعة منها ما هو ضروري نتيجة لظروف طارئة، مثل الكوارث الطبيعية، والحروب و..، ومنها ما هو غير ضروري في معظم الأحيان، كالنفقات المبالغ فيها متمثلة في المباني الفاخرة، والاحتفالات .. وغيرها من النفقات التي تتحمل عبئها الموازنة العامة، أما العامل الثاني فيتمثل في انخفاض معدلات نمو الإيرادات العامة من جهة أخرى. تهدف الدراسة إلى الوقوف على مشكلة تمويل عجز الموازنة العامة من خلال الوقوف على الوسائل التي اعتمدتها الدولة العباسية في معالجة العجز المالي ودورها في سد العجز ومعالجته، ونظراً لتعدد الوسائل التي اعتمدت من قبل الدولة العباسية في تمويل العجز المالي فقد اقتصر البحث على دراسة البعض منها وسوف نتناول البعض الاخر في بحث اخر، وقد افرد لكل منها مبحثاً خاصا بها، فضلاً عن المقدمة والخاتمة، والوسائل هي: أولاً: سك النقود الجديدة (الإصدار النقدي الجديد). ثانياً: القروض العامة ودورها في تمويل العجز. ثالثاً: التوظيف (فرض ضرائب جديدة غير الشرعية). فضلاً عن إيضاح مدى مشروعية هذه الوسائل والأدوات وما هي الشروط والضوابط الشرعية التي يتوجب توفرها عند التطبيق، وهل كان تطبيقها من قبل الدولة وفق تلك الضوابط والشروط.

A new class of tamoxifen analogues, using McMurry reaction conditions, is described. The scheme involved the conversion of ketoprofen (6) into amide derivatives 7 and 8, by coupling with N1,N1-substituted propan-1,3-diamine derivatives in the presence DIC and HOB. Treatment of 7 and 8 with various ketones under McMurry reaction conditions afforded the tamoxifen analogues 9–16. All the analogues were screened in vitro for their aromatase inhibitory and antiproliferative activity against MCF-7 breast cancer cells. Compounds 10, 11 and 12 showed a potent activity against MCF-7 cell lines breast cancer with IC50 values of 0.070, 0.042 and 0.077 µM of selectivity index (SI) 3.0, 2.5 and 2.6, respectively. Further, 12 exhibited potent activity against estrogen receptor (14.7 ± 2.4 nM), while compound 10 was the most active analogues against aromatase with IC50 of (0.070 nM). Furthermore, all new compounds were docked into human placental aromatase enzyme and estrogen receptor and showed very good correlations with experimental IC50. Therefore, we can consider these designed compounds as starting scaffold to design an efficient drug against estrogen receptor and aromatase. Communicated by Ramaswamy H. Sarma

Background: The plant-derived bioflavonoid amentoflavone has many important biological activities, among them remarkable antiviral effects, even against severe acute respiratory syndrome Coronavirus (SARS-CoV). It inhibits severe acute respiratory syndrome coronavirus (SARS-CoV) with an IC50 value of 8.3 M. (TMPRSS-2 activity is now thought to be the only factor necessary for cell entry and viral pathogenesis). In comparison, 3CLPRO is needed for COVID-19 replication and maturation during its life cycle. Aim: This study aims to perform an in silico study on amentoflavone activity against structural and non-structural severe acute respiratory syndrome coronavirus (SARS-CoV)-2 3-chymotrypsin-like protease (3CLPRO) and human transmembrane protease serine 2 (TMPRSS-2) proteins. Materials and Methods: Molecular docking studies were carried out using compounds against 3CLPRO and TMPRSS-2 proteins through the Swiss model, Uniport, PROCHECK, Swiss PDB viewer, PyMol, PyRx, and Desmond (Schrodinger package) computerized software.

Given the importance of cyclin-dependent kinases (CDKs) in the maintenance of cell development, gene transcription, and other essential biological operations, CDK blockers have been generated to manage a variety of disorders resulting from CDK irregularities. Furthermore, CDK9 has a crucial role in transcription by regulating short-lived anti-apoptotic genes necessary for cancer cell persistence. Addressing CDK9 with blockers has consequently emerged as a promising treatment for cancer. This study scrutinizes the effectiveness of nature-derived compounds (geniposidic acid, quercetin, geniposide, curcumin, and withanolide C) against CDK9 through computational approaches. A molecular docking study was performed after preparing the protein and the ligands. The selected blockers of the CDK9 exerted reliable binding affinities (−8.114 kcal/mol to −13.908 kcal/mol) against the selected protein, resulting in promising candidates compared to the co-crystallized ligand (LCI). The binding affinity of geniposidic acid (−13.908 kcal/mol) to CDK9 is higher than quercetin (−10.775 kcal/mol), geniposide (−9.969 kcal/mol), curcumin (−9.898 kcal/mol), withanolide C (−8.114 kcal/mol), and the co-crystallized ligand LCI (−11.425 kcal/mol). Therefore, geniposidic acid is a promising inhibitor of CDK9. Moreover, the molecular dynamics studies assessed the structure–function relationships and protein–ligand interactions. The network pharmacology study for the selected ligands demonstrated the auspicious compound–target–pathway signaling pathways vital in developing tumor, tumor cell growth, differentiation, and promoting tumor cell progression. Moreover, this study concluded by analyzing the computational approaches the natural-derived compounds that have potential interacting activities against CDK9 and, therefore, can be considered promising candidates for CKD9-induced cancer. To substantiate this study’s outcomes, in vivo research is recommended.

Bioactive compounds found in plants also have pharmacological antiviral effects. Berberine (BBR), an alkaloid found naturally in plants, is one of the phytochemicals with a wide range of biological activities, including antiviral, anticancer, anti-inflammatory and anti-inflammatory. In this study, we firstly aimed to predict pIC50 values for selcted compounds and then extract the binding patterns of berberine and its derivatives in the Sars Cov-2 Master Protease structure via employing molecular docking approache. Our results showed that berberine and its derivatives have good binding affinities towared Sars Cov2 main protease protein. Based on docking results the pharamaccokinetic studies for berberine, berberrubine, demethylen-berberine, jatrorrhizin, and thalifendine, were conducted and showed a good pharamacokinetic properties as an oral drugs. For deep inspection, we utiilized molecular dynmaics simulation to examine the Sars Cov2 main protease-ligand stabilities. The molecular dynamics simulation and PCA investigations revealed that thalifendine have a strong willing to act as good bindinder to SARS-CoV-2 protease. Further, the network based pharamacology showed that these drugs mediate different pathways such as human T-cell leukemia virus 1 infection, viral carcinogenesis, human immunodeficiency virus 1 infection, kaposi sarcoma-associated herpesvirus infection and epstein-Barr virus infection.The findings of this study have an important recomendation for thalifendine for more in vivo and in vitro studies to work. Communicated by Ramaswamy H. Sarma

In silico studies are attracting considerable interest due to their ability to understand protein–ligand interactions at the atomic level. The main principal tools of this in silico analyses are mo...

The current global epidemic of the novel coronavirus (SARS-CoV-2) has been labeled a global public health emergency since it is causing substantial morbidity and mortality on daily basis. We need to identify an effective medication against SARS-CoV-2 because of its fast dissemination and re-emergence. This research is being carried out as part of a larger strategy to identify the most promising therapeutic targets using protein-protein interactions analysis. Mpro has been identified as one of the most important therapeutic targets. In this study, we did in-silico investigations to identify the target and further molecular docking, ADME, and toxicity prediction were done to assess the potential phyto-active antiviral compounds from

This research is a recent effort to explore some new heterocyclic compounds as novel and potential nonstructural protein-16-nonstructural protein-10 (Nsp16-Nsp10) inhibitors for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inhibition. The SARS-CoV-2 is causative agent of coronavirus disease 2019 (COVID-19) pandemic. A set of 58 molecules belongs to the naphthyridine and quinoline derivatives have been recently synthesized and considered for structure-based virtual screening against Nsp16-Nsp10. Molecular docking was virtually performed to screen for anti-SARS-CoV-2 activity against Nsp16-Nsp10. Fourteen out of fifty-eight compounds were exhibited binding affinity higher than co-crystal bound ligand s-adenosylmethionine (SAM) toward Nsp16-Nsp10. Further, the in silico pharmacokinetics assessment was carried out and it was found that two molecules possess the acceptable pharmacokinetic profile, hence considered promising Nsp16-Nsp10 inhibitors. The binding interaction analysis was revealed some crucial binding interactions between the final selected two molecules and ligand-binding amino acid residues of Nsp16-Nsp10 protein. In order to explore the characteristics of the protein-ligand complex and how selected small molecules retained inside the receptor cavity in dynamic states, all-atoms conventional molecular dynamics (MD) simulation was performed. Several factors were obtained from the MD simulation trajectory evidently suggested the potentiality of the molecules and stability of the protein-ligand complex. Finally, the binding affinity of both molecules and SAM was explored through the MM-GBSA approach which explained that both molecules possess strong affection towards the Nsp16-Nsp10. Hence, from the pharmacoinformatics assessment, it can be concluded that both heterocyclic compounds might be crucial for SARS-CoV-2 inhibition, subjected to experimental validation.Communicated by Ramaswamy H. Sarma.

This study contains the synthesis, spectral analysis, and the enzyme inhibition effects of the Pd-based complexes bearing both 2-aminopyridine and N-heterocyclic carbene (NHC) ligands. The NHC ligand in the Pd-based complexes contains the 3-cyanobenzyl group. All new complexes were synthesized from (NHC)PdBr2(pyridine) complexes and 2-aminopyridine. These new complexes were characterized by using elemental analysis, 1H NMR, 13C NMR, and FT-IR spectroscopy techniques. Furthermore, inhibitor effects of these complexes were also tested toward some metabolic enzymes such as carbonic anhydrase and xanthine oxidase enzymes. The IC50 range for hCA I, hCA II, and XO were determined as 0.325–0.707, 0.238–0.636, and 0.576–1.693 μM, respectively. These data showed that Pd(II)–NHC complexes bearing 2-aminopyridine may be potent inhibitors of hCA and XO enzymes. Besides these applications, molecular docking was performed by using CDOCKER tool as a part of Discovery studio 2019, not only to determine the binding mode of synthesized inhibitors, but also to determine the correlation between the CDOCKER score values and IC50 values. We found a good correlation (R2 = 0.7403) between IC50 and the CDOCKER score of the inhibitors for XO. These findings could be a reference to start the development of effective medicine for XO.

Amygdalin possesses anticancer properties and induces apoptosis. Based on experimental studies the presence of amygdalin with cancer cells led to activate the caspase-3 and BAX and inhibits Bcl-2 and Poly (ADP-ribose) polymerase-1 (PARP-1) but without deep information on action mode of these activities. Herein, we leaped forward to examine the molecular dynamics of the bound amygdalin and free ligand proteins, to identify precise action (conformation changes in targeted proteins) of amygdalin through using double docking and molecular dynamics (MD) simulations for 50 ns time scale. The MD simulations revealed that the binding of amygdalin led to disrupting the interaction between the Bcl-2/BAX complex. We furthermore conducted MD simulation for Bcl-2/amygdalin to investigate the stability of the complex which is responsible for inhibition of Bcl-2. It has been obtained a stable Bcl-2/amygdalin complex during the 50 ns. The results give a detail explanation of how amygdalin activates BAX and inhibits Bcl-2. For caspase-3, the matter is different, we found that amygdalin led to disrupting the interaction of caspase-3’s two chains for intervals during 50 ns and then bind together repeatedly. The mechanism of caspase-3’s activation through switching by disrupt the interacts for periodic intervals manner. For PARP-1, the dynamics simulations results indicated amygdalin interacts with PARP-1’s binding site and forms stable interaction during simulation to render it inactive. Hence, amygdalin revealed a supernatural behavior through the MD simulations: it revealed a further clarification of the mystery amygdalin’s experimental action which can act as a multifunctional drug in the cancer therapeutics. Communicated by Ramaswamy H. Sarma

This paper reports a comprehensive study on the behavior of concavely curved soffit reinforced concrete (RC) beams strengthened in flexure with carbon fiber-reinforced polymer (CFRP) compo...

The current global epidemic of the novel coronavirus (SARS-CoV-2) has been labeled a global public health emergency since it is causing substantial morbidity and mortality on daily basis. We need to identify an effective medication against SARS-CoV-2 because of its fast dissemination and re-emergence. This research is being carried out as part of a larger strategy to identify the most promising therapeutic targets using protein-protein interactions analysis. Mpro has been identified as one of the most important therapeutic targets. In this study, we did in-silico investigations to identify the target and further molecular docking, ADME, and toxicity prediction were done to assess the potential phyto-active antiviral compounds from Justicia adhatoda as powerful inhibitors of the Mpro of SARS-COV-2. We also investigated the capacity of these molecules to create stable interactions with the Mpro using 100 ns molecular dynamics simulation. The highest scoring compounds (taraxerol, friedelanol, anisotine, and adhatodine) were also found to exhibit excellent solubility and pharmacodynamic characteristics. We employed MMPBSA simulations to assess the stability of docked molecules in the Mpro binding site, revealing that the above compounds form the most stable complex with the Mpro. Network-based Pharmacology suggested that the selected compounds have various modes of action against SARS-CoV-2 that include immunoreaction enrichment, inflammatory reaction suppression, and more. These findings point to a promising class of drugs that should be investigated further in biochemical and cell-based studies to see their effectiveness against nCOVID-19. Communicated by Ramaswamy H. Sarma

Dengue fever is a dangerous infectious endemic disease that affects over 100 nations worldwide, from Africa to the Western Pacific, and is caused by the dengue virus, which is transmitted to humans by an insect bite of Aedes aegypti. Millions of citizens have died as a result of dengue fever and dengue hemorrhagic fever across the globe. Envelope (E), serine protease (NS3), RNA-directed RNA polymerase (NS5), and non-structural protein 1 (NS1) are mostly required for cell proliferation and survival. Some of the diterpenoids and their derivatives produced by nature possess anti-dengue viral properties. The goal of the computational study was to scrutinize the effectiveness of diterpenoids and their derivatives against dengue viral proteins through in silico study. Methods: molecular docking was performed to analyze the binding affinity of compounds against four viral proteins: the envelope (E) protein, the NS1 protein, the NS3 protein, and the NS5 protein. Results: among the selected drug candidates, triptolide, stevioside, alepterolic acid, sphaeropsidin A, methyl dodovisate A, andrographolide, caesalacetal, and pyrimethamine have demonstrated moderate to good binding affinities (−8.0 to −9.4 kcal/mol) toward the selected proteins: E protein, NS3, NS5, and NS1 whereas pyrimethamine exerts −7.5, −6.3, −7.8, and −6.6 kcal/mol with viral proteins, respectively. Interestingly, the binding affinities of these lead compounds were better than those of an FDA-approved anti-viral medication (pyrimethamine), which is underused in dengue fever. Conclusion: we can conclude that diterpenoids can be considered as a possible anti-dengue medication option. However, in vivo investigation is recommended to back up the conclusions of this study.

The present study attempted to scrutinize the protective effect of the methanolic extract of P. chaba stem bark against paracetamol-induced hepatotoxicity in Sprague-Dawley rats, along with the gas chromatography-mass spectrometry (GC-MS) analysis to identify phytochemicals, which were further docked in the catalytic site of CYP2E1 and the MD simulation for system that plays a major role in the bio-activation of toxic substances that produce reactive metabolites, leading to hepatotoxicity. P. chaba stem methanol extract (250 and 500 mg/kg) were treated orally with the negative control and the negative control silymarin (50 mg/kg) groups. Phytochemical profiling was conducted using GC-MS. In in-silico studies, PyRx software was used for docking analysis and the stability of the binding mode in the target active sites was evaluated through a set of standard MD-simulation protocols using the Charmm 27 force field and Swiss PARAM. Co-administration of P. chaba at both doses with APAP significantly reduced the APAP-augmented liver marker enzymes ALT, AST, ALP, and LDH, along with serum albumin, globulin, hepatic enzymes, histopathological architecture, lipid profiles, total protein, and total bilirubin, and elevated the levels of MDA. The GC-MS analysis indicated that P. chaba extract is enriched in fatty acid methyl esters (46.23 %) and alkaloids (10.91 %) and piperine is represented as a main phytochemical. Among all the identified phytochemicals, piperine (-8.0 kcal/mol) was found to be more interacting and stable with the binding site of CYP2E1. Therefore, all of our findings may conclude that the P. chaba stem extract and its main compound, piperine, are able to neutralize APAP-induced hepatic damage.

A novel infectious agent, SARS-CoV-2, is responsible for causing the severe respiratory disease COVID-19 and death in humans. Spike glycoprotein plays a key role in viral particles entering host cells, mediating receptor recognition and membrane fusion, and are considered useful targets for antiviral vaccine candidates. Therefore, computational techniques can be used to design a safe, antigenic, immunogenic, and stable vaccine against this pathogen. Drawing upon the structure of the S glycoprotein, we are trying to develop a potent multi-epitope subunit vaccine against SARS-CoV-2. The vaccine was designed based on cytotoxic T-lymphocyte and helper T-lymphocyte epitopes with an N-terminal adjuvant

Fiber-reinforced polymers (FRPs) are widely used to enhance the flexural capacity of existing concrete structures subjected to various loading actions. However, when FRPs are applied to st...

This paper investigates the performance of curved soffit reinforced concrete beams strengthened in flexure with carbon fiber reinforced polymers (CFRPs) under static loading. The effect of...

Shigella dysenteriae type 1 is considered as an epidemic in different developing countries, which is responsible for the most severe form of bacterial dysentery. It habitually can develop to the most severe form of dysentery with deadly complications. Development of drugs against this disease is still ongoing. Therefore, we used in silico studies to screen the Inula britannica phytocompounds that are used in traditional Chinese and Kampo Medicines and have activities against different diseases. Spinacetin, eupatin, chrysoeriol and diosmetin were successfully passed through the docking-based screening and absorption, distribution, metabolism, excretion and toxicity (ADMET) filtration. The estimated docking affinities of eupatin, diosmetin, chrysoeriol and spinacetin with Dihydrofolate reductase type 1 (DHFR-1), were −6.5, −6.5, −6.3 and −6.1 kcal/mol, respectively. Which were selected for further investigations based on their favorable ADME/Tox characteristics. Then, the 100 ns molecular dynamics (MD) simulations of apo DHFR, spinacetin-DHFR, eupatin-DHFR, chrysoeriol-DHFR and diosmetin-DHFR complexes were carried out. The RMSD fluctuations of the spinacetin, eupatin, chrysoeriol and diosmetin inside the binding site were explored. Subsequently, the effect of binding Spinacetin, eupatin, chrysoeriol and diosmetin upon the dynamic stability of protein was assessed. Additionally, Principal Component Analysis (PCA) and Hydrogen bond analysis was performed for the apo protein and the protein ligand complexes. The results revealed that chrysoeriol and eupatin has good inhibitory effects against DHFR-1 as treatment for Shigella dysenteriae type when compared to other compounds under study. Hence this study implies that eupatin and chrysoeriol are a significantly potential drug like molecule for the treatment of Shigellosis and must undergo validation through in vivo and in vitro experiments. Communicated by Ramaswamy H. Sarma

Gastric cancer (GC) has limited effective treatment options and is followed up with biomarkers that have insufficient sensitivity and specificity. Recent studies on Collagen Type X Alpha 1 Chain (COL10A1) show that the COL10A1 gene may be a diagnostic and/or prognostic biomarker for different cancer types. Moreover, its relationship with the Sex determining Region Y (SRY)-related High-Mobility Group (HMG) box (SOX9) gene which is also a transcription factor, was discovered recently, and co-expression of these two genes are associated with the development of GC. However, to the best of our knowledge, there is no study in the literature on how potential damaging mutations in the SOX9 and COL10A1 genes can affect their interactions. The aim of this study is to investigate the interactions of wild-type and potentially damaging mutated structures of COL10A1 and SOX9 genes. Thus, outputs for drug development and therapeutic strategies for GC can be obtained. For this purpose, structure validation and energy minimization analyses as well as docking and binding affinity calculations were performed. As a result, it was found that all investigated mutations (P563S, I588L, T624A, H165R and N110T) increased the binding affinity between the COL10A1-SOX9 complex, especially the N110T and H165R mutants in SOX9. As a conclusion, the N110T and H165R mutants in SOX9 may contribute to tumor progression. Therefore, it is important to consider these mutations for future therapeutic strategies.Communicated by Ramaswamy H. Sarma.

The levels of reactive oxygen species (ROS) are tightly controlled and regulated by Nuclear Factor Erythroid-2-Like 2 (Nrf2) transcription factor, which is the main regulator of antioxidant responses and its suppressor protein Kelch-like ECH-associated protein 1 (Keap1). Our previous study has identified six novel changes in Nrf2/Keap1 pathway in pediatric ALL, which were described for the first time. These changes in the pathway are likely to alter the evolutionary process of amino acids and cause structural changes in the final products of genes. In this study, we aimed to compare the pathogenicity of eight determined mutations reported in our previous study by utilizing different programs with different algorithms and molecular dynamics simulation. Since it is too difficult to handle each existing mutation in a wet laboratory

SARS-CoV-2 is a new generation of coronavirus, which was first determined in Wuhan, China, in December 2019. So far, however, there no effective treatment has been found to stop this new generation of coronavirus but discovering of the crystal structure of SARS-CoV-2 main protease (SARS-CoV-2 Mpro) may facilitate searching for new therapies for SARS-COV-2. The aim was to assess the effectiveness of available FDA approved drugs which can construct a covalent bond with Cys145 inside binding site SARS-CoV-2 main protease by using covalent docking screening. We conducted the covdock module MMGBSA module in the Schrodinger suite 2020-1, to examine the covalent bonding utilizing. Besides, we submitted the top three drugs to molecular dynamics simulations via Gromacs 2018.1. The covalent docking showed that saquinavir, ritonavir, remdesivir, delavirdine, cefuroxime axetil, oseltamivir and prevacid have the highest binding energies MMGBSA of –72.17, −72.02, −65.19, −57.65, −54.25, −51.8, and −51.14 kcal/mol, respectively. The 50 ns molecular dynamics simulation was conducted for saquinavir, ritonavir and remdesivir to evaluate the stability of these drugs inside the binding pocket of SARS-CoV-2 main protease. The current study provides a powerful in silico results, means for rapid screening of drugs as anti-protease medications and recommend that the above-mentioned drugs can be used in the treatment of SARS-CoV-2 in combined or sole therapy. Communicated by Ramaswamy H. Sarma

Cell-division protein kinases (CDKs) are gorgeous examples of targets for the helpful treatment of cancer by using multi-target inhibitors. Specifically, targeting cell-division protein kinase1/cyclin B (CDK1/Cyclin B), cell-division protein kinase 2/cyclin A (CDK2/Cyclin A) and cell-division protein kinase 4/cyclin D1 (CDK4/Cyclin D1) are considered a safe strategy to over the toxicity complications which are emerging from low specificity. In this work, we conducted the double docking and molecular dynamics to explicate the effect of amygdalin upon conformational modifications of selected targets. Moreover, the principal component analysis (PCA) was employed to inspect the effect of amygdalin on the fundamental motions of the each protein as target. Docking results illustrated that the binding free energies of amygdalin (AMY) to CDK1/Cyclin B, CDK 2/Cyclin A and CDK 4/Cyclin D1 were to be −9.41, −9.02 and −10.6 kcal/mol, respectively. The PCA results disclosed that binding of the AMY minimized the fundamental dynamics of CDK1/Cyclin B and CDK2/Cyclin A. The obtained results can give an insight into inhibitory activity of amygdalin that could help in designing of potential inhibitors. In the other word, it can be used AMY to inhibit other mechanisms and/or hallmarks of cancer. Communicated by Ramaswamy H. Sarma

Background and objective Historically, amygdalin has been used as alternative medicine or in vitro and in vivo studies, but no single study exists which discusses the structural mechanism of amygdalin at a molecular level. This paper inquiries into the inhibitory actions of amygdalin on the selected targets: AKT1, FAK, and ILK, which are regulators for various mediated signaling pathways, and are associated with cell adhesion, migration, and differentiation. In order to get details at the molecular level of amygdalin's inhibitory activities against chosen proteins, molecular modeling and simulation techniques including double docking, molecular dynamics simulation, free energy landscape analysis, and binding free energy calculation were exerted. Methods To get molecular level details of amygdalin inhibitory effects against the relevant proteins; here the utilized tools are the following: the double docking, molecular dynamics simulation, free energy landscape analysis, g_mmpbsa, and interaction entropy were used to evaluate the inhibitory activity against targeted proteins. Results The computational calculations revealed that amygdalin inhibits the selected targets via block the ATP-binding pocket of AKT1, FAK, and ILK by forming stable hydrogen bonds. Moreover, free energy landscape, FEL exposed that amygdalin stabilized the global conformations of both FAK and ILK proteins to the minimum global energy besides it reduced the essential dynamics of FAK and ILK proteins. MMPBSA computations provided further evidence for amygdalin's stability inside the ATP-binding pocket of AKT1, FAK, and ILK with a binding free energy of 45.067, −13.033, 13.109 kJ/mol, respectively. The binding free energies are lastly consistent with the hydrogen bonding and pairs within 0.35 nm results. The decomposition of binding energy shows the pivotal amino acid residues responsible for the stability of amygdalin's interactions inside the ATP-binding sites by forming hydrogen bonds. Conclusions Before this work, it was enigmatic to make predictions about how amygdalin inhibits metastasis of cancer. But the computational results contribute in several ways to our understanding of amygdalin activity and provide a basic insight into the activity of amygdalin as a multi-target drug in the metastasis and invasion of cancer.

The research aimed to investigate the anti-inflammatory effect of 4-hydroxy coumarin derivatives on inflammatory response in rats and to estimate the toxicity of enumerated compounds (3-11) following acute exposure. Toxicity report was collected by oral dosing administered individually to rats on a scale of 10-3000 mg/kg, while an indication of toxicity was observed for ten days following the last given dose. The response to inflammation was estimated using the model of xylene-induced edema and the model of carrageenan-inflammation of the paw. Compounds were administered orally to animals at a once-daily dose for seven sequential days. Molecular docking studies with COX-II enzyme were used to explain deeply the activity of synthesized compounds. Furthermore, the in-silico results were quite consistent with biological activity. Interestingly, compounds 5 and 10 showing the highest binding points (lower values). Therefore, the molecular dynamics simulation study of the most active compounds 5 and 10 was performed.

ملخص البحث: تسعى هذه الدراسة إلى تتبع استدعاء الشخصيات التراثية من دينية وتاريخية في تجربة الشاعر محمد القيسي الشعريّة، وذلك لإظهار دورها في توجيه دلالات النصّ، وتفعيل إيقاعه، بتلك المثيرات البصرية التي تفعّل الدفقة الشعريّة، وتغلفها بالطابع الدراميّ. وقد سارت الدراسة لتوضيح ذلك في ثلاثة مستويات: الأول يبحث في الاندماج الكلي ما بين الشخصية المـُستدعاة والواقع، والثاني في التأثير الجزئي لهذه الشخصيات، أما الثالث فيكون في النفي الكلي أو القلب لما هي عليه الشخصية التراثية؛ ولذلك فقد أسهم هذا الاستدعاء في خلق حركة مراوغة بين الشكل والمضمون في تجربة الشاعر محمد القيسي. توصل البحث إلى أن ظاهرة استدعاء الشخصيات التراثية من أهم الظواهر التي أثْرت القصيدة المعاصرة، وأسهمت في تشكيل رؤيا الشاعر اتجاه قضايا عصره، وحددت مواقفه المعبرة عن واقعه؛ لذا ربطته علاقة قوية وفاعلة بالتراث، تنم عن وعيه بموروثه الإنساني الشامل والزاخر بمصادره؛ لتعزز بذلك دلالات وجماليات متعددة. الكلمات المفتاحية: الشخصية- التراث- استدعاء- دلالة- الواقع. Abstract The study attempts to trace the technique of recalling traditional religious and historical figures in the poem of Muhammad al-Qaisi with respect to its function in implying the textual meaning and activating its rhythm through the visual stimulus that sensitize the poetic aesthetic and embrace it with dramatic feature. The study does this in three stages: first it discusses in the total metamorphosis between the invoked character and the reality, second, in the partial effect of these characters; and thirdly, total denial or the reversal of what used to be the experience of those characters. The recalling of those characters had contributed in circumventing between form and content in the poetic experience of Muhammad al-Qaisi. The study concludes that recalling traditional characters is among the most important phenomenon that has influenced modern poetry and contribute in forming the vision of the poet about the issues of his time and shape his positions that are expressive of his reality. This had helped to forge a strong relation with the tradition derived from his awareness and his human heritage that is comprehensive and rich with resources to consolidate the various aesthetical meanings. Keywords: Characters, Tradition, Recalling, Meaning, Reality Abstrak Kajian ini mencuba untuk mengesan teknik mengenang kembali figura budaya, agama dan sejarah dalam syair nukilan Muhammad al-Qaysi berkaitan fungsinya dalam memberikan bayangan makna tekstual dan menggiatkan iramanya melalui rangsangan visual yang mencetuskan nilai estetika syair dan merangkuminya dengan ciri yang dramatik. Kajian ini dilaksanakan dalam tiga tahap: pertama ia membicarakan tentang metamorphosis total antara watak yang dibayangkan itu dan reality; keduanya, ia membicarakan tentang kesan yang dibawa watak tersebut; ketiga, mengetengahkan penafian menyeluruh atau rekaan semula ciri dan situasi watak tersebut. Penggunaan watak dan figura tersebut telah berjaya mengimbangkan di antara bentuk dan kandungan syair yang dinukilkan Muhammad al-Qaysi. Kajian ini mendapati penampilan watak-watak lama ini merupakan satu teknik yang telah menyumbang dalam mewarnai syair-syair moden dan membantu membentuk persepsi penyair terhadap isu era beliau juga pendirian beliau yang diluahkan berdasarkan realiti yang dialami. In itelah membantu juga dalam mengukuhkan hubungan di antara budaya dan kesedaran beliau serta kahazanah kemanusiaan beliau yang menyeluruh dan kaya dengan sumber-sumber yang dapat menyerlahkan lagi nilai estetika dalam karya-karya yang dinukilkan. Kata kunci: Watak-watak, Tradisi, Mengenang kembali, Makna, realiti

Background: Depressive disorder is a recurrent illness that affects large numbers of the general population worldwide. In recent years, the goal of depression treatment has moved from symptomatic response to that of full remission. However, treatment-resistant depression is a major challenge in the treatment of depression or depression-related disorders. Consensus opinion, therefore, suggests that effective combined aggressive initial treatment is the most appropriate strategy. Objectives: This study aimed to evaluate the effects of quercetin (QUR) and/or ascorbic acid (AA) on Phenobarbital-induced sleeping mice. Methods: QUR (50 mg/kg) and/or AA (25 mg/kg) with or without intraperitoneally pre-treated with GABA receptor agonist (diazepam: 2 mg/kg, i.p.) or antagonist (Flumazenil: 2.5 mg/kg, i.p.) to underscore the effects, as well as the possible involvement of the GABA receptor in the modulatory action of QUR and AA in sleeping mice. Additionally, an in silico study was undertaken to predict the involvement of GABA receptors in the sleep mechanism. Results: Findings suggest that the pretreatment of QUR and AA modulated the onset and duration of action of the standard drugs in experimental animals. The acute administration of QUR and/or AA significantly (p &lt, 0.05) reversed the DZP-mediated onset of action and slightly reversed the duration of sleep time in comparison to the vehicle (control) group. A further combination of QUR or AA with the FLU resulted in an enhancement of the onset of action while reducing the duration of action, suggesting a FLU-like effect on the test animals. In in silico studies, AA and QUR showed good to moderate binding affinities with GABAA and GABAB receptors. Conclusions: Both QUR and AA produced a stimulatory-like effect on mice, possibly through the GABAA and GABAB receptor interaction pathways. Further studies are necessary to verify this activity and clarify the exact mechanism of action(s) involved.

This study focused on synthesis various dimethyl N-benzyl-1H-1,2,3-triazole-4,5-dicarboxylate and (N-benzyl-1H-1,2,3-triazole-4,5-diyl)dimethanol derivatives under the conditions of green chemistry without the use of solvent and catalysts. Their inhibition properties were also investigated on xanthine oxidase (XO) activity. All dimethanol and dicarboxylate derivatives exhibited significant inhibition activities with IC50 values ranging from 0.71 to 2.25 μM. Especially, (1-(3-bromobenzyl)-1H-1,2,3-triazole-4,5-diyl)dimethanol (5c) and dimethyl 1-(4-chlorobenzyl)-1H-1,2,3-triazole-4,5-dicarboxylate (6 g) compounds were found to be the most promising derivatives on the XO enzyme inhibition with IC50 values 0.71 and 0.73 μM, respectively. Moreover, the double docking procedure was to evaluate compound modes of inhibition and their interactions with the protein (XO) at atomic level. Surprisingly, the docking results showed a good correlation with IC50 [correlation coefficient (R2 = 0.7455)]. Also, the docking results exhibited that the 5c, 6f and 6 g have lowest docking scores −4.790, −4.755, and −4.730, respectively. These data were in agreement with the IC50 values. These results give promising beginning stages to assist in the improvement of novel and powerful inhibitor against XO.