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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
Tue Jul 01 2014
Journal Name
Bulletin Of The Iraq Natural History Museum (p-issn: 1017-8678 , E-issn: 2311-9799)
SEDIMENTARY STUDY OF SHIRANISH FORMATION AT HIJRAN SECTION- NORTH IRAQ
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    Shiranish has been studied at Hijran section near Erbil city, NE Iraq. Fifty two thin-sections were prepared to study them under polarized microscope, to determine the petrographic component, organic content and digenetic processes. Rock units subdivided into four rock beds, as follows: dolostone, foraminiferal biomicrite, poorly washed biomicrite and micrite. Vertical succession of Shiranish Formation refers to off-shore quite marine environment.

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Publication Date
Mon Dec 11 2017
Journal Name
The First Mohesr And Hced Iraqi Scholars Conference In Australasia
Creep Strain Development of Self-compacting Portland-Limestone Cement Concrete
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Prediction of the structural response of reinforced concrete to the time-dependent, creep and shrinkage, volume changes is complex. Creep is usually determined by measuring the change, with time, in the strain of specimens subjected to a constant stress and stored under appropriate conditions. This paper brings into view the development of creep strain for four self-compacting concrete mixes: A40, AL40, B60 and BL60 (where 40 and 60 represent the compressive strength level at 28 days and L indicates to Portlandlimestone cement). Specimens were put under sustained load and exposed to controlled conditions in a creep chamber (ASTM C512). The test results showed that normal strength Portland-limestone mixes have yielded lower ultimate c

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Publication Date
Fri Sep 06 2024
Journal Name
Journal Of Economics And Administrative Sciences
Comparison of Some Wavelet Transformations to Estimate Nonparametric Regression Function
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The purpose of this article is to improve and minimize noise from the signal by studying wavelet transforms and showing how to use the most effective ones for processing and analysis. As both the Discrete Wavelet Transformation method was used, we will outline some transformation techniques along with the methodology for applying them to remove noise from the signal. Proceeds based on the threshold value and the threshold functions Lifting Transformation, Wavelet Transformation, and Packet Discrete Wavelet Transformation. Using AMSE, A comparison was made between them , and the best was selected. When the aforementioned techniques were applied to actual data that was represented by each of the prices, it became evident that the lift

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Publication Date
Sun Jan 01 2017
Journal Name
Iraqi Journal Of Agricultural Sciences
Response of different cucumber hybrids to grafting on squash rootstock
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Publication Date
Wed Aug 03 2016
Journal Name
Technology Reports Of Kansai University
Some statistical results for solution type of the Inequalities system
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Publication Date
Tue Dec 03 2024
Journal Name
African Journal Of Biological Sciences
Antibacterial effect of plantago major extract on staphylococcus aureus biofilm
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The ability of microorganisms to attach to living and non-living surfaces and create a biofilm is the cause of numerous long-lasting illnesses, as well as their strong resistance to drugs. Bacterial biofilms consist of intricate assemblies of immobile bacteria. These are located in an extracellular matrix and adhere to various surfaces for a long period. The present study evaluated the antibacterial effectiveness of Plantago major extract against Staphylococcus aureus biofilm. The specimens analyzed in this investigation were skin infections of clinical origin. The current study was not previously studied, particularly in terms of S. aureus biofilm breakdown and inhibition. The disc diffusion method was used to test the antimicrobial activi

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Publication Date
Tue Nov 20 2012
Journal Name
J. Of University Of Anbar For Pure Science
Laser Processing For Nanoscale Size Quantum Wires of AlGaAs/GaAs
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In this work we investigate and calculate theoretically the variation in a number of optoelectronic properties of AlGaAs/GaAs quantum wire laser, with emphasis on the effect of wire radius on the confinement factor, density of states and gain factor have been calculated. It is found that there exist a critical wire radius (rc) under which the confinement of carriers are very weak. Whereas, above rc the confinement factor and hence the gain increase with increasing the wire radius.

Publication Date
Mon Jul 29 2024
Journal Name
Earth And Environmental Science
Refinement of Internal-Combustion Engine Oil Properties Via Magnetic Flux
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To verify the influence of magnetic flux on the characteristics of SAE 10W-30 gasoline engine oil when the engine oil is exposed to different magnetic fluxes 0, 6, 9, and 13 Volt. The following oil characteristics were measured: viscosity at 40 and 100 °C, and total acid number (TAN) mg KOH/g. The research was carried out in a completely randomized design with three replications for each treatment under the 5% probability level to compare the means of the treatments. The results of the experiment showed that there were significant differences in the studied properties when the engine oil was exposed to the above magnetic fluxes and, inversely, especially the magnetic flux of 13 Volt, which led to a decrease in the viscosity of the oils at

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Publication Date
Thu Mar 01 2012
Journal Name
Al-khwarzmi Engineering Journal
Dynamic response analysis for the parabolic trough of solar collector
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parabolic trough

Publication Date
Sun Mar 12 2017
Journal Name
Al-academy
Reality design Arabic letters for the purposes of digital programming
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Arabic calligraphy has great importance in the printing designs that are often on the written character-based to perform functional goals and to achieve some of the aesthetic values ​​in design work, has led major developments in the field of computer manufacturing and design software for the design and layout to increase to deal with the programmed character for the purposes of typesetting has confronted this Find the Arab character programmed for the purposes of typesetting for the detection of the most important design interventions that underwent the Arabic letter written to turn it into a programmed image intended for the purposes of the printing and typesetting has been addressed in the context of which the theoretical types of

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