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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 20 2024
Journal Name
Journal Of Petroleum Research And Studies
Advanced Machine Learning application for Permeability Prediction for (M) Formation in an Iraqi Oil Field
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Permeability estimation is a vital step in reservoir engineering due to its effect on reservoir's characterization, planning for perforations, and economic efficiency of the reservoirs. The core and well-logging data are the main sources of permeability measuring and calculating respectively. There are multiple methods to predict permeability such as classic, empirical, and geostatistical methods. In this research, two statistical approaches have been applied and compared for permeability prediction: Multiple Linear Regression and Random Forest, given the (M) reservoir interval in the (BH) Oil Field in the northern part of Iraq. The dataset was separated into two subsets: Training and Testing in order to cross-validate the accuracy

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Publication Date
Mon Jun 15 2026
Journal Name
Opera Med Physiol
A COMPARATIVE STUDY OF CITRIC ACID FROM ASPERGILLUS NIGER AND CITRUS LIMON ON CYTOGENETIC, IMMUNOLOGICAL, AND HEPATOPROTECTIVE PARAMETERS IN ALBINO MICE
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This study compared the effects of citric acid (CA) derived from microbial fermentation using Aspergillus niger (400 mg kg-1) and natural extraction from Citrus limon (400 mg kg1) in albino mice. Parameters assessed included cytogenetic damage via the micronucleus (MN) assay, immunological response through immunoglobulin (IgA, IgG, IgM) titers, and hepatoprotective activity based on liver enzyme levels (AST, ALT, ALP) and histopathological inves tigation. Mice were divided into six groups (n=10/group) as follows: (1) negative control, (2) carbon tetrachloride (CCl₄ 0.02%), (3) lemon CA, (4) A. niger, (5) CCl₄ + lemon CA, and (6) CCl₄ + A. niger CA. The CCl4 group exhibited a significantly higher MN frequency (0.06 ± 0.008) compa

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Publication Date
Sun Dec 30 2012
Journal Name
Al-kindy College Medical Journal
Evaluation of Fludarabine, and granulocyte colony stimulating factor in treatment of efractory/Relapsed Acute Leukemias in adult Iraqi patients
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Background: Refractory/relapsed acute leukemia has always been a challenging problem for hematologist. Over the past decade emphasis has been made in the development of regimens containing fludarabine, combined with cytosine arabinoside for the treatment of refractory/relapsed acute leukemias. The aim of this study is to evaluate the efficacy and toxicity of the combination of fludarabine, high dose cytarabine, and granulocyte colony stimulating factor in refractory relapsed cases of acute leukaemia,
Methods: a prospective study is being conducted at the national center of hematology and hematology unit /Baghdad teaching hospital from July 2008 to July 2010.Twenty Patients with refractory/relapsed acute leukemia were treated with flud

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Publication Date
Fri Jan 01 2021
Journal Name
Water Pollution And Management Practices
Existence of Antibiotics in Wastewater as a Pollution Indicator
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Publication Date
Thu Apr 01 2021
Journal Name
Iop Conference Series: Earth And Environmental Science
Disadvantages of using Nano-particles as fertilizers in Iraq
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Abstract<p>The agriculture around the world faced many difficulties and the important was to reduce inputs of chemical fertilizers and pesticides and increase the total yield specially with the continuous grow of populations numbers at the world expected to reach more than 9 billion by 2050. In other hand there are other problems which make the challenges bigger such as wars, biotic and abiotic stress, and diseases. The scientists tried to find solutions by using Nano-fertilization which consider a modern way to quickly grow up the yield and decrease use the chemicals. The use of nanotechnology may be destructive on human and the environment due to fast accumulation in the tissues of alive bodie</p> ... Show More
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Publication Date
Fri Aug 09 2024
Journal Name
Theory And Practice In Language Studies
Fallacy as a Strategy of Argumentation in Political Debates
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This study aims to study argumentation in political debates by figuring out the logical fallacies employed in the debates of Clinton and Trump, the presidential nominees of the 2016 elections, and Biden and Trump, the leading contenders in the 2020 United States presidential election. The study attempts to answer the questions: (1) What relevance fallacies are adopted in the debate between Trump and Clinton? (2) What rhetorical devices are used to influence the audience and gain voters besides fallacies in the debates selected? The study analyses two texts from two arguments using Damer's (2009) taxonomy of relevance fallacy and rhetorical devices based on Perrine’s (1969) model of communication and interpersonal rhetoric to answe

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Publication Date
Tue Mar 20 2018
Journal Name
Day 3 Thu, March 22, 2018
Economics of Supramolecular Assemblies as Displacement Fluids in EOR
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Abstract<p>It is estimated that over the next few decades, EOR will be used for the more than 50% of oil production in the US and worldwide. From these, in reservoir with viscositites ranging between 10 – 150 mPa.s, polymer flooding is suggsted as the EOR method. Therefore, there is an upper limit to the recommended range of reservoir oil viscosities for polymer flooding. To address the issue of this limitation of polymer injectivity and pumping efficiency, we propose a novel method. The method involves the use of Supramolecular Systems, which are composed of long-chain aminoacids and maleic acids post complexation. Their unique feature of resersible viscosities allows the operator to overcome</p> ... Show More
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Publication Date
Sun Mar 02 2008
Journal Name
Baghdad Science Journal
Effect of Volatile Oil of Myrtus communis on growth and activities of some types of Pathogenic Bacteria and Candida albicans
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This Study aimed to studying the effect of Volatile oil extracted from the leaves of Myrtus communis on the growth and activities of the following types of bacteria: Staphylococcus aureus, Streptococcus pyogenes, Klebsilla pneumoniae, Pseudomonas aeruginosa, and the yeast Candida albicans. The results showed an inhibitory effect of the oil on both the growth and activity of the tested microbes. This was reflected by the minimum inhibitory concentration (MIC) of Staphylococcus aureus, Streptococcus pyogenes, Klebsilla pneumoniae, Pseudomonas aeruginosa which was: (2.5, 1.25, and 2.5,5 % respectively), and the yeast (5) %. Also, the Minimum bactericidal concentration (MBC) to the bacteria mentioned above was (5, 2.5,5,10 % respectivel

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Publication Date
Sun Oct 15 2023
Journal Name
Sumer 3
Treatment of shallow and deep white spot lesions with three different mouthwashes evaluated by laser fluorescence (an in vitro study)
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This research aims to find how three different types of mouthwashes affect the depth of artificial white spot lesions. Teeth with various depths of white spot lesions were immersed in either splat mouthwash, Biorepair mouthwash, Sensodyne mouthwash, or artificial saliva (control)twice daily for one minute for 4 weeks and 8 weeks at 37°C. After this immersion procedure, lesion depth was measured using a diagnosed pen score. A one-way analysis of variance, Dunnett T3 and Tukey's post hoc α = .05 were used to analyze the testing data. Splat mouthwash enhanced the WSL remineralization and made the lowest ΔF compared with other mouthwashes in shallow and deep enamel after 4 and 8 weeks of treatment. In the repair groups, after 4 weeks

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Publication Date
Sun Mar 13 2011
Journal Name
Baghdad Science Journal
The Effect of Silybum marianum L. aquatic crude extracts on the cancer cell lines and normal cell line in vitro
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The aquatic crude extract of Silybum marianum dry grains prepared by melting them in distil water by the method of soak and shake. The effect of Silybum marianum crude extract studied in vitro on three tumor cell line the Hep-2, AMN-3 and RD for 24, 48 and 72 hours of exposure, and one cell line of normal cells REF for 72 hr exposure. The results showed that the prescence of toxic effect of the aquatic crude extract on the cell lines of Hep-2, AMN-3 and RD at 10 and 100 µg/ ml upto the higher concentrations when they exposed to the extract for 48 hr. as compared with the control treatment, and when the exposure period increased to 72 hr. the toxic effect started at low concentrations (5 and 10 µg/ ml) as compared with the control g

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