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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
Fri Jan 04 2019
Journal Name
Drinking Water Engineering And Science Discussions
The Ability of Froth Formed without Chemicals to Hold Bacteria
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Abstract. Froth flotation is a solid-liquid separation technique that uses hydrophobicity as a driving force. Bacteria and other drinking water microorganisms tend to be hydrophobic and can be removed from water using this application. The biggest limitation against using froth flotation in the drinking water industry is the difficulty of producing froth without chemical frothers and holding bacteria in this froth without chemical collectors which deteriorate water taste and odor. Recently, researchers at the University of Sheffield described a method for producing froth using only water and compressed air. This has enabled froth flotation to be studied as an alternative to biocides for the removal of bacteria from drinking water. T

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Publication Date
Fri Jul 01 2016
Journal Name
Al–bahith Al–a'alami
A Semiotic Approach to the Analysis of the News Story
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This study attempts to provide an approach analysis for the news, depending on the bases and principles which conceptuality semiotic researchers of this field first of them «A. J. Gremas» for the theory of «narrative discourse analysis», to more clarify we tried to apply it on a published press- news, to concludes the most important steps and methods that are necessary to follows gain more understanding of the press- news.

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Publication Date
Sun Mar 01 2020
Journal Name
Journal Of Engineering
Thermal Performance Analysis of Compact Heat Exchangers for Thermoelectric Generators
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The efficiency of internal combustion engines (ICE) is usually about thirty percent of the total energy of the fuel. The residual energy is lost in the exhaust gas, the lubrication, and the cooling water in the radiators. Recently much of the researcher’s efforts have focused on taking advantage of wasted energy of the exhaust gas. Using a thermoelectric generator (TEG) is one of the promising ways. However, TEG depends entirely on the temperature difference, which may be offered by the exhaust muffler. An experimental test has been conducted to study the thermal performance of a different muffler internal design. The researchers resort to the use of lost energy in an ICE using TEG, which is one of the ways to take adv

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Publication Date
Wed Sep 24 2025
Journal Name
Dijlah Journal Of Medical Sciences P-issn:3078-3178, E-issn:3078-8625
pdf Review Article Biochemical Impact of Trace Elements on Metabolism
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Numerous trace elements, notably metals, are essential for the normal functioning of several biological reactions, especially as enzyme cofactors. Several Trace elements refer to essential micronutrients required in minimal quantities for certain biological functions pertaining to human metabolism, albeit their minimal concentrations in the organism. Nonetheless, our understanding of this topic is considerably restricted, and emerging insights into their metabolic functions necessitate contributions and have implications across various domains, encompassing nutritional chemistry, with a focus on analytical chemistry, biological sciences, medicine, pharmacology, and agricultural sciences. 

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Publication Date
Tue Jun 14 2016
Journal Name
Al-academy
The impact of modern global art movements on Graphic Design
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The significant shift in the Fine Arts, who led the avant-garde movements and creative which appeared in the modern, specifically in the mid-nineteenth century and early twentieth century era path, embodied in a clear show of new aesthetic value rejects traditional methods put in shape and color qualities She described the movements subjectivity or no formal, was intended to determine the direct function of expression and speech language in the visual arts away from the representation and simulation of reality was accompanied by the appearance of those fine movements directed towards a global approach to design carries features and clear in its organizations formalism of the most important move away from the symmetry and the adoption of

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Publication Date
Mon Jun 19 2023
Journal Name
Journal Of Engineering
Behavior of Reinforced Gypseous Soil Embankment Model under Cyclic Loading
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The construction of embankment for roadway interchange system at urban area is restricted due to the large geometry requirements, since the value of land required for such construction is high, and the area available is limited as compared to rural area. One of the optimum solutions to such problem is the earth reinforcement technique which requires a limited area for embankment construction. Gypseous soil from Al-Anbar governorate area was obtained and subjected to various physical and chemical analysis to determine it is properties. A laboratory model box of 50x50x25 cm was used as a representative embankment; soil has been compacted in five layers at maximum dry density (modified compaction) and an aluminum reinforcement strips were i

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Publication Date
Mon Jan 01 2018
Journal Name
Iraqi Journal Of Agricultural Sciences 49 (4), 632-638‏
Influence of some organic fertilizers on date palm CV. Barhi
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Publication Date
Tue May 05 2020
Journal Name
Book
Study the inhibitory effect of miswak extract on biofilm gene.
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This book presents the problem of tooth decay due to bacteria Streptococcus mutans one of methods of treatment using 3 extracts of S. persica (miswak) (aqueous, acetone and methanol) and prove its effectiveness and its impact on the gtf (B, C, and D) genes that code the glucosyltransferase (Gtf) enzymes that cause decay membrane compared to the usual means used for the prevention of tooth decay

Publication Date
Sun Apr 30 2023
Journal Name
Iraqi Geological Journal
Pore Structure Characterization of Shale Reservoir Using Nitrogen Adsorption-Desorption
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This research paper aimed to quantitively characterize the pore structure of shale reservoirs. Six samples of Silurian shale from the Ahnet basin were selected for nitrogen adsorption-desorption analysis. Experimental findings showed that all the samples are mainly composed of mesopores with slit-like shaped pores, as well as the Barrett-Joyner-Halenda pore volume ranging from 0.014 to 0.046 cm3/ 100 g, where the lowest value has recorded in the AHTT-1 sample, whereas the highest one in AHTT-6, while the rest samples (AHTT-2, AHTT-3, AHTT-4, AHTT-5) have a similar average value of 0.03 cm3/ 100 g. Meanwhile, the surface area and pore size distribution were in the range of 3.8 to 11.1 m2 / g and 1.7 to 40 nm, respectively.

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Publication Date
Tue Jun 18 2024
Journal Name
Al-bahir Journal For Engineering And Pure Sciences
Organization of Traffic on the Main Streets Microcontroller Traffic Lights
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