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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
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 Oct 23 2018
Journal Name
Journal Of Economics And Administrative Sciences
The role of financial derivatives on the risk of foreign currency exchange volatility in enhancing the quality of profits - a method that is prescribed in the Iraqi environment
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The objective of this research is to develop a method for applying financial derivatives in the local environment to reduce the risk of foreign exchange rate fluctuations to enhance quality of accounting profits through Financial reporting to local units In accordance with international financial reporting standards, To accomplish this objective was selected a sample of Iraqi units exposed to the risk of fluctuations in foreign currency rates, As the research found:

  • many companies and banks in the local environment a lot of losses due to fluctuations in foreign currency exchange rates.
  • that financial derivatives in the Iraqi environment represent

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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
Mon Feb 25 2019
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
Using Classification of Brown risks in Evaluation of the internal control system: Application Research in Karbala University
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Internal control system is a safety valve that preserves economic units assets and ensure the accuracy of financial data, as well as to obligation in the laws, regulations, administrative policies ,and improve the efficiency, effectiveness and economic of operation, so it has become imperative for these units attention to internal and developed control system The research problem in exposure the economic units when the exercise of their business to many of the risks to growth or hinder the achievement of its objectives and the risks (financial, operational, strategy, risk) and not it rely on risk Assessment according to modern scientific methods, as in Brown's risk Classification, Which led to the weakness of the internal control identif

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Publication Date
Sun Jun 05 2016
Journal Name
Baghdad Science Journal
Biochemical Characterization for Lipid Synthesis in Aspergillus niger
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A niger, a fungus which doesn't have high ability to production lipid, this fungus has been select to investigate the non oleaginicity. In this search, there are explorations about: i) growth profile ii) enzymes profile iii) isoforms. Growth profile shows that this fungus doesn't have ability to accumulate lipid more than 6% while bio mass are around 10g/l in spite of the presence of glucose in the media till the end of cultivation time and excision of nitrogen within 24 hrs. In enzyme study, we investigate all lipogenic enzymes Malic enzyme (ME), Fatty acid synthase (FAS), ATP: Citrate lays (ACL), NAD+ isocitrate dehydrogenase (NAD+ICDH), Glucose-6-phosphate (G6PD), and 6-phosphogluconate dehydrogenase (6PGD), all these enzymes show, ac

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Publication Date
Thu Nov 08 2018
Journal Name
Iraqi National Journal Of Nursing Specialties
Studying the Effect of Different Separating Medium on the Roughness of the tissue surface of Acrylic Denture Base (In Vitro Study)
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Objective: In order to evaluate the effect of different typed of Separating Medium on the roughness of the fitted
tissue surface of acrylic denture base.
Methodology: Chosen three types of separating medium (Group A Tin foil), (Group B Detery Isolant),(Group C
Cold Mould Seal),used 30 samples of hot cure acrylic resin ,10 samples for each group, after complete curing of
these samples , Profilometer device was used to measure the surface roughness of each sample in all groups.
Results: Using One Way ANOVA Test and LSD test, the results were highly significant in differences among all
groups. Although (Group A) showing lest roughness, (Group B) showing a satisfactory result of roughness, While
(Group C) Showing the hig

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Publication Date
Tue Feb 17 2026
Journal Name
Journal Of Baghdad College Of Dentistry
The effects of various beverages on the shear bond strength of light-cured orthodontic composite (An in vitro comparative study)
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Background: This study was conducted to assess the effects of various beverages on the shear bond strength of light-cured orthodontic composite used to bond stainless steel orthodontic brackets on human teeth and to determine the site of bonding failure of this material. Materials and Methods: Fifty extracted human premolars were selected and randomly divided into five equal groups each with 10 teeth according to the beverage type (Control, One Tiger, Milk, Green tea and Coffee). After bonding, the teeth were immersed in specific beverages for 5 minutes twice daily with equal intervening intervals then washed and stored in distilled water at 37º C for the reminder of the day. The process was carried out for 30 days. The samples were then

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Publication Date
Tue Feb 17 2026
Journal Name
Journal Of Baghdad College Of Dentistry
The influence of recent adhesive onlay fabrication techniques on the fracture resistance of endodontically treated premolars (An in vitro study)
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Background: Endodontically treated teeth have low resistance to fracture against occlusal forces. The strengthening effect of bonded esthetic onlay restoration on weakened tooth has been reported. This study aimed to assess the fracture resistance of endodontically treated premolars restored with composite with and without cuspal coverage by using direct and indirect techniques. Indirect technique done by CAD/CAM system (computer aided design –computer aided manufacturer) and laboratory processing. Material and methods: Forty human extracted maxillary premolars of approximately comparable sizes were divided into four groups: Group (A): Ten endodontically treated teeth directly filled with Filtek Z250xt without cuspal coverage. Group

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Publication Date
Mon Mar 13 2017
Journal Name
Journal Of Baghdad College Of Dentistry
Testing Different Properties of A Light-Cured Denture Base Material After Addition of Silicon Oxide Nanofiller (An in Vitro Study)
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ABSTRACT Background: Improving the properties of heat- cured and self-cured acrylic resin have been studied by many researchers. However, little studies concerned with visible light cured resin (VLCR) improved through addition of nanofiller are available. The purpose of this study was to evaluate some properties of (VLCR) after addition of SiO2 nanofiller. Materials and Methods: SiO2 nanofiller were added to (VLCR) tray material after being dissolved in tetrahydrofuran (THF) solvent. According to the pilot study 2% SiO2 nanofiller addition exhibited better properties than the other percentages (1%, 3%). The main study conducted involved (100) specimens divided into 5 groups according to the test included. (20) Specimens were selecte

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