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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
Thu Jun 15 2017
Journal Name
Pakistan Journal Of Nutrition
Effect of Adding Dietary Conjugated Linoleic Acid to Broiler Diets on Production Performance and Fatty Acid Content in Meat
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Conjugated Linoleic Acid (CLA) is an essential polyunsaturated omega fatty acid that occurs naturally in vegetable oils. It also plays an important role in preserving meat for longer periods by preventing oxidation of other fats. Thus, it can be used in the production of functional foods with high biological value and low cholesterol levels by adding poultry diets. Objective: The aim of the present study was to evaluate the effect of adding CLA to broiler diets on production performance and fatty acid content in the meat. Methodology: One-day-old Ross-308 chicks were randomly distributed into four dietary treatment groups: control (0 g CLA kgG1 diet; A1), 0.5 g CLA kgG1 diet (A2), 0.75 g CLA kgG1 diet (A3) and 1 g CLA kgG1 diet (A4). Diets

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Publication Date
Thu Dec 28 2023
Journal Name
Journal Of Physical Education
The reality of the administrative values of sports activities in the Faculties of the University of Baghdad from the point of view of leaders and those related to the divisions and units of student's activities
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The research aimed to identify the level of reality of administrative values of sports activities in the Faculties of the university of Baghdad from the point of view of the leaders and those related to the divisions and units of student's activities and the case study method was adopted from the descriptive approach.

Publication Date
Thu Jan 24 2019
Journal Name
Journal Of Education College Wasit University
Postmodernism and Technology in Don Delillo's Novel The White Noise
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This paper aims at investigating the effect of postmodernism and technology on the social life in Don Delillo's novel The White Noise. In this novel, Don Delillo portrays the chaotic life by using modern technology which has been presented by three ways. The first way is by television as being a source of information and entertainment. The second way is by the toxic event whereas the third is by Dylar's episode and its destructive consequences. He depicts that through the atmosphere of Jack's family plus its effects on the life and thoughts of the elders and society. He proves that technology is leading humanity not to safety, but to death. He further highlights that by showing the impact of technology on the life of the main charac

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Publication Date
Thu Feb 07 2019
Journal Name
Iraqi Journal Of Laser
Evaluation of 532 nm Q-Switched Nd:YAG Laser and Acid Etching of Class V Composite Restoration: Comparative Histological Study
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Laser etching may be an alternative to acid etching of enamel and dentin. Several characteristics of irradiated dental hard tissues have been considered advantageous, microscopically rough surfaces without demineralization, open dentinal tubules without smear layer production and dentin surface sterilization. The aim of this study is to determine and compare histology the microleakage in class V cavity restored with a light cured composite after conditioning the samples(tooth surface) with 1-acid etching, 2-Q-switched Nd:YAG Laser etching and finally 3- acid and laser etching. Materials and methods: Twenty four non carious human extracted teeth were used in this study. The samples were equally grouped into four groups of six teeth each.

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Publication Date
Sun Oct 22 2023
Journal Name
مجلة الدراسات المستدامة
Strategies, Techniques and Activities Used by English Language Teachers in Employing Online Teaching
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Publication Date
Mon Mar 30 2009
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Prediction of bubble size in Bubble columns using Artificial Neural Network
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In the literature, several correlations have been proposed for bubble size prediction in bubble columns. However these correlations fail to predict bubble diameter over a wide range of conditions. Based on a data bank of around 230 measurements collected from the open literature, a correlation for bubble sizes in the homogenous region in bubble columns was derived using Artificial Neural Network (ANN) modeling. The bubble diameter was found to be a function of six parameters: gas velocity, column diameter, diameter of orifice, liquid density, liquid viscosity and liquid surface tension. Statistical analysis showed that the proposed correlation has an Average Absolute Relative Error (AARE) of 7.3 % and correlation coefficient of 92.2%. A

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Publication Date
Fri May 01 2020
Journal Name
Journal Of Engineering
Semi-Analytical Prediction of Flank Tool Wear in Orthogonal Cutting of Aluminum
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This study aims to model the flank wear prediction equation in metal cutting, depending on the workpiece material properties and almost cutting conditions. A new method of energy transferred solution between the cutting tool and workpiece was introduced through the flow stress of chip formation by using the Johnson-Cook model. To investigate this model, an orthogonal cutting test coupled with finite element analysis was carried out to solve this model and finding a wear coefficient of cutting 6061-T6 aluminum and the given carbide tool.

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Publication Date
Mon May 01 2017
Journal Name
Journal Of Stored Products Research
Detection and prediction of Sitophilus oryzae infestations in triticale via visible and near-infrared spectral signatures
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Triticale is a hybrid of wheat and rye grown for use as animal feed. In Florida, due to its soft coat, triticale is highly vulnerable to Sitophilus oryzae L. (rice weevil) and there is interest in development of methods to detect early-instar larvae so that infestations can be targeted before they become economically damaging. The objective of this study was to develop prediction models of the infestation degree for triticale seed infested with rice weevils of different growth stages. Spectral signatures were tested as a method to detect rice weevils in triticale seed. Groups of seeds at 11 different levels (degrees) of infestation, 0–62%, were obtained by combining different ratios of infested and uninfested seeds. A spectrophotometer wa

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Publication Date
Sun Dec 01 2019
Journal Name
Saudi Medical Journal
The diagnostic power of circulating micro ribonucleic acid 34a in combination with cancer antigen 15-3 as a potential biomarker of breast cancer
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Publication Date
Sun Sep 01 2019
Journal Name
Transylvanian Review
Metacongnitive Thinking Skills Implied in Questions and Activities of Computer Textbook for the Fifth Grade Preparatory
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The research aims to know the availability of supra-cognitive thinking skills in the questions and activities of the computer book for the fifth grade preparatory scientific and literary branches in Iraq for the academic year 2018/2019, as the researcher has prepared a list of supra-cognitive thinking skills included two areas and (6) key skills and (27) A sub - skill, where by the questions and activities of the aforementioned authors were analyzed. The researcher followed the descriptive analytical approach "method of content analysis", and adopted the explicit and implicit unit of analysis, as was verified the validity and stability of the analysis, and the results showed unevenness and imbalance in the distribution of supra-cognitive th

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