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Synthesis, In Silico Prediction, and In Vitro Evaluation of Anti-tumor Activities of Novel 4'-Hydroxybiphenyl-4-carboxylic Acid Derivatives as EGFR Allosteric Site Inhibitors
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Introduction:

Allosteric inhibition of EGFR tyrosine kinase (TK) is currently among the most attractive approaches for designing and developing anti-cancer drugs to avoid chemoresistance exhibited by clinically approved ATP-competitive inhibitors. The current work aimed to synthesize new biphenyl-containing derivatives that were predicted to act as EGFR TK allosteric site inhibitors based on molecular docking studies.

Methods:

A new series of 4'-hydroxybiphenyl-4-carboxylic acid derivatives, including hydrazine-1-carbothioamide (S3-S6) and 1,2,4-triazole (S7-S10) derivatives, were synthesized and characterized using IR, 1HNMR, 13CNMR, and HR-mass spectroscopy.

Results:

Compound S4 had a relatively high pharmacophore-fit score, indicating that it may have biological activity similar to the EGFR allosteric inhibitor reference, and it scored a relatively low ΔG against EGFR TK allosteric site, indicating a high likelihood of drug-receptor complex formation. Compound S4 was cytotoxic to the three cancer cell lines tested, particularly HCT-116 colorectal cancer cells, with an IC50 value comparable to Erlotinib. Compound S4 induced the intrinsic apoptotic pathway in HCT-116 cells by arresting them in the G2/M phase. All of the new derivatives, including S4, met the in silico requirements for EGFR allosteric inhibitory activity.

Conclusion:

Compound S4 is a promising EGFR tyrosine kinase allosteric inhibitor that warrants further research.

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Publication Date
Tue Feb 21 2017
Journal Name
Biomechanics And Modeling In Mechanobiology
A novel method for non-invasively detecting the severity and location of aortic aneurysms
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The influence of an aortic aneurysm on blood flow waveforms is well established, but how to exploit this link for diagnostic purposes still remains challenging. This work uses a combination of experimental and computational modelling to study how aneurysms of various size affect the waveforms. Experimental studies are carried out on fusiform-type aneurysm models, and a comparison of results with those from a one-dimensional fluid–structure interaction model shows close agreement. Further mathematical analysis of these results allows the definition of several indicators that characterize the impact of an aneurysm on waveforms. These indicators are then further studied in a computational model of a systemic blood flow network. This demonstr

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Publication Date
Fri Feb 01 2019
Journal Name
Journal Of Economics And Administrative Sciences
Adopting IPSASs and its impact on the quality of financial reporting and performance evaluation in Iraqi government units
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Abstract

     Performance evaluation is of great importance in all countries of the world, because it has a prominent and effective role in determining the efficiency and effectiveness of the optimal use of available resources, which are rare and important in achieving the desired objectives. With the continued growth of public spending and the limited resources, the State seeks to achieve its objectives through its units with minimal expenditure or deficit, rationality and wastefulness in the spending. In many countries, particularly developing countries, reforms are made in the public sector to achieve that goal through the adoption of IPSAS, which is reflected in the developmen

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Publication Date
Sat Jul 30 2016
Journal Name
Hepatology
Farnesoid X receptor activation increases reverse cholesterol transport by modulating bile acid composition and cholesterol absorption in mice
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Activation of farnesoid X receptor (FXR) markedly attenuates development of atherosclerosis in animal models. However, the underlying mechanism is not well elucidated. Here, we show that the FXR agonist, obeticholic acid (OCA), increases fecal cholesterol excretion and macrophage reverse cholesterol transport (RCT) dependent on activation of hepatic FXR. OCA does not increase biliary cholesterol secretion, but inhibits intestinal cholesterol absorption. OCA markedly inhibits hepatic cholesterol 7α‐hydroxylase (Cyp7a1) and sterol 12α‐hydroxylase (Cyp8b1) partly through inducing small heterodimer partner, leading to reduced bile acid pool size and al

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Publication Date
Sun Jan 20 2019
Journal Name
Iraqi Journal Of Market Research And Consumer Protection
EVALUATION OF SOME BIOChEMICAL LEVELS IN THE SERUM OF PROFESSORS EXPOSED TO CHEMICALS IN THE LABORATORIES OF THE UNIVERSITY OF SAMARRA: EVALUATION OF SOME BIOChEMICAL LEVELS IN THE SERUM OF PROFESSORS EXPOSED TO CHEMICALS IN THE LABORATORIES OF THE UNIVERSITY OF SAMARRA
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A chemical study was carried out to evaluate the efficiency of the liver enzyme concertation and uric acid level and its antagonists in the serum of the professors exposed to chemicals in the laboratories of the University of Samarra and their comparison with the healthy people. The research included 25 samples of the exposed professors and 20 samples as a group of officers.

              The results of the current study showed a significant increase in the level of   AST, ALT in the serum of professors exposed to chemicals compared to healthy people. The results showed no significant increase in

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Publication Date
Sun Jun 30 2024
Journal Name
Lark
The Image of the Arab in Hebrew Literature for Young Adults – A Reading of the Novel “Nadia” by Kalila Ron Feder
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يهدف هذا البحث الى التطرق الى صورة العربي كما يعرضها ادب اليافعين العبري في رواية " نادية " للكاتبة العبرية " كاليلا رون فيدر " . والتي تعد من الاديبات العبريات اللواتي تطرقن بصورة مباشرة الى موضوع ما خلف الجدار ، والصراع العربي – الإسرائيلي وانعكاساته على المجتمع الإسرائيلي بصورة عامة والمجتمع العربي بصورة خاصة . ينقسم هذا البحث إلى ثلاثة فصول، تطرق الفصل الأول  إلى "ادب اليافعين"، و تاريخه ، مميزاته والفئ

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Publication Date
Wed Mar 13 2024
Journal Name
Journal Of Robotics
Hierarchical Stabilization and Tracking Control of a Flexible-Joint Bipedal Robot Based on Anti-Windup and Adaptive Approximation Control
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Bipedal robotic mechanisms are unstable due to the unilateral contact passive joint between the sole and the ground. Hierarchical control layers are crucial for creating walking patterns, stabilizing locomotion, and ensuring correct angular trajectories for bipedal joints due to the system’s various degrees of freedom. This work provides a hierarchical control scheme for a bipedal robot that focuses on balance (stabilization) and low-level tracking control while considering flexible joints. The stabilization control method uses the Newton–Euler formulation to establish a mathematical relationship between the zero-moment point (ZMP) and the center of mass (COM), resulting in highly nonlinear and coupled dynamic equations. Adaptiv

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Publication Date
Tue Sep 01 2020
Journal Name
Baghdad Science Journal
A Comparative Study on the Active Constituents, Antioxidant Capacity and Anti-Cancer Activity of Cruciferous Vegetable Residues
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This study is pointed out to estimate the effectiveness of two solvents in the extraction and evaluating the active ingredients and their antioxidant activity as well as anti-cancer efficiency. Therefore, residues from four different Brassica vegetables viz. broccoli, Brussels sprout, cauliflower, and red cherry radish were extracted using two procedures methods: methanolic and water crude extracts. Methanol extracts showed the highest content of total phenolic (TP), total flavonoids (TF), and total tannins (TT) for broccoli and Brussels sprouts residues. Methanolic extract of broccoli and Brussels sprouts residues showed the highest DPPH· scavenging activity (IC50 = 15.39 and 18.64 µg/ml). The methanol and water ex

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Publication Date
Fri Dec 20 2024
Journal Name
Iraqi Journal Of Pharmaceutical Sciences
Genetic Polymorphisms at TNF-Alpha Receptors Associated some Autoimmune Diseases and Response of Anti-TNF Biologics: Review
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Some genetic factors are not only involved in some autoimmune diseases but also interfere with their treatment, Such as Crohn's disease (CD), Rheumatoid Arthritis (RA), ankylosing spondylitis (AS), and psoriasis (PS). Tumor Necrosis Factor (TNF) is a most important pro-inflammatory cytokine, which has been recognized as a main factor that participates in the pathogenesis and development of autoimmune disorders. Therefore, TNF could be a prospective target for treating these disorders, and many anti-TNF were developed to treat these disorders. Although the high efficacy of many anti-TNF biologic medications, the Patients' clinical responses to the autoimmune treatment showed significant heterogeneity. Two types of TNF receptor (TNFR); 1 an

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Publication Date
Sat Apr 20 2024
Journal Name
Baghdad Science Journal
Synthesis Catalyst of Loading Nano Platinum on Graphene Nanosheets and Photodegradation of Bromophenol blue in Ultra-violet light.
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تم في هذا البحث استخدام المحفز الجديد المصنع من تحميل دقائق البلاتين النانوية على سطح الصفائح النانوية للكرافين كمحفز ضوئي واختباره لدراسة التجزئة الضوئية لملوثات المياه وازالتها بشكل نهائي من مصادر المياه لما لها من تأثير سلبي على البيئة. حيث تم استخدام صبغة البروموفينول الأزرق كمثال على أحد الملوثات. في البدء تم التأكد من تحضير المحفز بالطريقة المستخدمة في طريقة العمل من خلال تشخيصه باستخدام عدد من ا

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Publication Date
Fri Nov 01 2024
Journal Name
Baghdad Science Journal
Synthesis Catalyst of Loading Nano Platinum on Graphene Nanosheets and Photodegradation of Bromophenol blue in Ultra-violet light.
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تم في هذا البحث استخدام المحفز الجديد المصنع من تحميل دقائق البلاتين النانوية على سطح الصفائح النانوية للكرافين كمحفز ضوئي واختباره لدراسة التجزئة الضوئية لملوثات المياه وازالتها بشكل نهائي من مصادر المياه لما لها من تأثير سلبي على البيئة. حيث تم استخدام صبغة البروموفينول الأزرق كمثال على أحد الملوثات. في البدء تم التأكد من تحضير المحفز بالطريقة المستخدمة في طريقة العمل من خلال تشخيصه باستخدام عدد من ا

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