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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
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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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
Thu Apr 11 2019
Journal Name
Political Sciences Journal
Scientific Activities College of branches
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Scientific Activities College of branches

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Publication Date
Sun Dec 01 2013
Journal Name
Political Sciences Journal
Activities of International Studies Branch
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نشاطات فرع الدراسات الدولية

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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
Sat Jun 01 2019
Journal Name
2019 International Engineering Conference (iec)
Assessment of Specific Absorption Rate and Temperature in the Tumor Tissue Subjected to Plasmonic Bow-Tie Optical Nano-Antenna
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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
Mon Jun 01 2009
Journal Name
Journal Of Economics And Administrative Sciences
Suggested method for modifying the site parameter
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     Estimating multivariate location and scatter with both affine equivariance and positive break down has always been difficult. Awell-known estimator which satisfies both properties is the Minimum volume Ellipsoid Estimator (MVE) Computing the exact (MVE) is often not feasible, so one usually resorts to an approximate Algorithm. In the regression setup, algorithm for positive-break down estimators like Least Median of squares typically recomputed the intercept at each step, to improve the result. This approach is called intercept adjustment. In this paper we show that a similar technique, called location adjustment, Can be applied to the (MVE). For this purpose we use the Minimum Volume Ball (MVB). In order

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Publication Date
Tue Sep 01 2020
Journal Name
Baghdad Science Journal
Modified Mathematical Model of Tumor Treatment by Radiotherapy
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In this research, a mathematical model of tumor treatment by radiotherapy is studied and a new modification for the model is proposed as well as introducing the check for the suggested modification. Also the stability of the modified model is analyzed in the last section.

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Publication Date
Wed Mar 25 2020
Journal Name
International Journal Of Drug Delivery Technology
Preparation, Characterization and In-Vitro Diffusion Study of Different Topical Flurbiprofen Semisolids
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Flurbiprofen (FLB) is chemically 2-(3- fluoro-4-phenyl phenyl) propanoic acid. It is a nonsteroidal anti-inflammatory drug (NSAID) used in the treatment of rheumatoid arthritis and osteoarthritis. Oral administration of this drug is associated with severe gastrointestinal side effects like ulceration and gastrointestinal bleeding. The solution to this problem lies in the fact that topically applied NSAIDs are safer than orally. This study aims to prepare different topical semisolid formulation of FLB as cream base (o/w), (w/o) and gel base using different gel-forming agents in different concentrations. Comparing characterization properties in addition to release and diffusion study for all the prepared formulas to select the best on

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