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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 Jan 01 2012
Journal Name
Ibn Al- Haitham J. Fo R Pure & Appl. Sci
Multiple Mixing Ratios of Gamma Rays From Reaction Using a2-ratio Method
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The -multiple mixing ratios of γ-transitions from levels of populated in the are calculated in the present work by using the a2-ratio methods. We used the experimental coefficient (a2) for two γ-transitions from the same initial state, the statistical tensor, which is related to the a2-coefficient would be the same for the two transitions. This method was used in a previous work for pure transitions or which can be considered pure. In these cases the multiple mixing ratios for the second transition ( ) equal zero, but in our work we applied this method for mixed γ-transitions and then the multiple mixing ratio ( ) is known for one transition. Then we calculate the ( ) value and versareversa. The weight average of the -values calcu

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Publication Date
Mon Oct 01 2012
Journal Name
Iraqi Journal Of Physics
Optical properties of TiO2 thin films prepared by reactive d.c. magnetron sputtering
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TiO2 thin films were deposited by reactive d.c magnetron sputtering method on a glass substrate with various ratio of gas flow (Oxygen /Argon) (50/50, 100/50 and 150/50) at substrate temperature 573K. It can be observe that the optical energy gap of TiO2 thin films dependent on the ratio of gas flow (oxygen/argon), it varies between (3.45eV-3.57eV) also it is seen that the optical constants (α, n, K, εr and εi ) has been varied with the change of the ratio of gas flow (Oxygen /Argon).

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Publication Date
Sun Sep 05 2010
Journal Name
Baghdad Science Journal
Design of six electrode Enzial electrostatic lens low aberrations for electron gun
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A computerized investigation has been carried out on the design of six electrodes electrostatic lenses used in electron gun application. The Finite-Element Method (FEM) was used in the solution of Laplace equation for determine the axial potential distribution. The electron trajectory under zero magnification condition. The optical properties, spherical and chromatic aberrations, the object and image focal length and object and image position are calculated. A very good futures for the electron gun with these lenses have been computed where are a beam current of 8.7*10-7A can be supplied using cathode tip of radius 10nm.

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Publication Date
Fri Nov 29 2019
Journal Name
Iraqi Journal Of Physics
Band Gap Characterization of Thermally Treated Hybrid Blend ZnPc/CdS Thin Films
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Spin coating technique used to prepare ZnPc, CdS and ZnPc/CdS blend thin films, these films annealed at 423K for 1h, 2h and 3h. Optical behavior of these films were examined using UV-Vis. and PL. The absorption spectrum of ZnPc shows a decreasing in absorption with the increase of annealing time while CdS spectrum give a clearly absorption peak at~510 nm. Energy gap of ZnPc increases from 1.41 to 1.52 eV by increasing the annealing time. Eg of CdS decrease by increasing annealing time, from 2.3 eV to 2.2 eV. The intensities of the peaks obtained from PL spectra were strongly dependent on annealing time and confirmed the results obtained from UV-Vis. D.C. conductivity measurement showed that all the thin films have two differen

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Publication Date
Mon May 20 2019
Journal Name
The Journal Of Engineering
Experimental comparison of two linear machines developed for the free piston engine
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: In this study, a linear synchronous machine is compared with a linear transverse flux machine. Both machines have been designed and built with the intention of being used as the power take off in a free piston engine. As both topologies are cylindrical, it is not possible to construct either using just flat laminations and so alternative methods are described and demonstrated. Despite the difference in topology and specification, the machines are compared on a common base in terms of rated force and suitability for use as a generator. Experience gained during the manufacture of two prototypes is described.

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Publication Date
Fri Jun 16 2023
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Optimization of Bis-anthraquinones Production from Endophytic Fungi Diaporthe sp. GNBP-10
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Bis-anthraquinones with a unique molecular backbone, (+)-2,2’-epicytoskyrin A (epi) and (+)-1,1′-bislunatin (bis), was produced by endophytic fungi Diaporthe sp GNBP-10 associated with Gambir plant (Uncaria gambier). Epi and bis possess robust antimicrobial activity toward various pathogens. This study focus on knowing the optimum condition of epi and bis production from Diaporthe sp GNBP-10. A series of culture media with various nutrient compositions was investigated in epi and bis production. The content of epi and bis was determined by measuring the area under the curve from TLC-densitometric (scanner) experiment. The linear regression analysis was then applied to obtain the results. The optimi

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Publication Date
Mon Jun 01 2015
Journal Name
Journal Of Engineering
Using Nanoparticles for Enhance Thermal Conductivity of Latent Heat Thermal Energy Storage
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Phase change materials (PCMs) such as paraffin wax can be used to store or release large amount of energy at certain temperature at which their solid-liquid phase changes occurs. Paraffin wax that used in latent heat thermal energy storage (LHTES) has low thermal conductivity. In this study, the thermal conductivity of paraffin wax has been enhanced by adding different mass concentration (1wt.%, 3wt.%, 5wt.%) of (TiO2) nano-particles with about (10nm) diameter. It is found that the phase change temperature varies with adding (TiO2) nanoparticles in to the paraffin wax. The thermal conductivity of the composites is found to decrease with increasing temperature. The increase in thermal conductivity ha

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Publication Date
Wed Jul 01 2020
Journal Name
Journal Of Engineering
Improvement the Mechanical Characteristics of Alloy Steel DIN 41Cr4 by Shot Peening
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The effects of shot peening treatment (SPT) were studied at (10,20, and 30) minutes on the rotating bending fatigue behavior and the behavior of the alloy steel DIN 41Cr4 vibrations. The hardness test, tensile test, constant amplitude fatigue tests, and the vibration measurements were performed on samples with and without cracks at room temperature (RT), also, the fracture surface was examined and analyzed by a Scanning Electron Microscope (SEM). The results of the investigations, for example, Stress to Number of cycles to failure (S-N) curves, fatigue strength improvement factor of 5% to 10%, the decreasing percentage of maximum Fast Fourier Transform (FFT) acceleration of the shot-peened condition were compared to untr

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Publication Date
Tue Jan 02 2018
Journal Name
Journal Of Educational And Psychological Researches
The effect of 5555 strategy on reading comprehension among 4th preparatory students
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The effect of 5555 strategy on reading comprehension among 4th preparatory students Assist. Prof. Dr. Hassan Khilbas Hammadi College of Education Ibn Rushd – The University of Baghdad Assistant Lecturer. Waleed Khaled Talib Directorate – General For Education Province Of AL - Anbar The purpose of study is to identify the effect of 5555 strategy on reading comprehension among 4th preparatory students. To do this, null hypothesis was postulated. The author hypothesize that there is no a statistically significant difference at (0.05) level between experimental group's scores who study reading comprehension subject following the 5555 strategy and control group's scores who study the same subject following the traditional method in readin

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Publication Date
Wed Jun 28 2023
Journal Name
The Iraqi Journal Of Veterinary Medicine
Antibacterial Activity of Lactiplantibacillus plantarum‎ from Dairy Products ‎Against Some ‎Foodborne Bacteria
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Lactiplantibacillus plantarum‎, one of lactic acid bacteria (LAB), is found in various foods, ‎‎including dairy products, meat, and vegetables, and most of these bacteria offer beneficial ‎‎effects to humans and animals as potential probiotics with broad-spectrum antimicrobial ‎‎activities. The aim of this study was evaluating the antibacterial efficacy of L. ‎plantarum‎ ‎against ‎some foodborne bacteria isolated from dairy products. This research involved 34 dairy ‎products, ‎including local and imported milk, cheese, and yogurt sold locally in Baghdad ‎province, Iraq, during May ‎‎2022. For the isolation of L. ‎plantarum‎, a special medium called ‎MRS (de Man Rogosa and ‎Sharpe) was applied. Colonie

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