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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
Sat May 01 2021
Journal Name
Journal Of Physics: Conference Series
Seismic performance of Al-wand earth dam: numerical analysis
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Abstract<p>The seismic can be threatened the stability of the flexible body of the earth dam and can cause completely damaged or deformation on their embankment. Therefore, a geotechnical engineer needs to know the effect of earthquakes on earth structures. The change in the seismic zone that recently Iraq affected is the reason for this research, in general, in 2017, the whole of Iraq, and in particular the region, where the Al-Wand earth dam (the subject of the study) is located, was exposed to several earthquakes. This research project mainly aims to study the behavior of Al-Wand earth dam under seismic load in different conditions by simulating Al-Wand earth dam through numerical modeling an</p> ... Show More
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Publication Date
Sat Jan 01 2022
Journal Name
Journal Of The Mechanical Behavior Of Materials
Reducing settlement of soft clay using different grouting materials
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Abstract<p>Different injection material types were tried in the injection of soft clay, such as lime (L), silica fume (SF), and leycobond-h (LH). In this study, experiments were made to study the effect of injection on soft clay consolidation settlement. A sample of natural soft clayey soil was investigated in the laboratory and the sample was injected with each of the grout materials used, L, SF, L + SF, and L + SF + LH. A 20 cm<sup>3</sup> of each slurry grout was conducted into the soil, which was compacted in California Bearing Ratio (CBR) mold and cured for 7 days, and then the sample was loaded to 80 N load by a circular steel footing 60 mm in diameter. The settlement was r</p> ... Show More
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Publication Date
Fri Apr 01 2022
Journal Name
Journal Of Engineering
Improvement of Diesel Fuel Engine Performance by Nanoparticles Additives
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This study was done to investigate the impact of different nanoparticles on diesel fuel characteristics, Iraqi diesel fuel was supplied from al-Dura refinery and was treated to enhance performance by improving its characteristics. Two types of nanoparticles were mixed with Iraqi diesel fuel at various weight fractions of 30, 60, 90, and 120 ppm. The diesel engine was tested and run at a constant speed of 1600 rpm to examine and evaluate the engine's performance and determine emissions. In general, ZnO additives' performance analysis showed they are more efficient for diesel fuel engines than CeO. The performance of engine diesel fuel tests showed that the weight fraction of nanoparticles at 90 and 120 ppm give a similar

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Publication Date
Fri Apr 01 2022
Journal Name
Baghdad Science Journal
On Cohomology Groups of Four-Dimensional Nilpotent Associative Algebras
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The study of cohomology groups is one of the most intensive and exciting researches that arises from algebraic topology. Particularly, the dimension of cohomology groups is a highly useful invariant which plays a rigorous role in the geometric classification of associative algebras. This work focuses on the applications of low dimensional cohomology groups. In this regards, the cohomology groups of degree zero and degree one of nilpotent associative algebras in dimension four are described in matrix form.

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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)
Pharmacological aspects of Borago officinalis (Borage): A review article
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Abstract:

Borago officinalis is highly interesting amongst nutritional and medical source relate to its high composition of some useful phytochemical compound. It is great plants with bright blue star-shaped flowers present in most world regions and usually known as borage. The Borago phytochemical analysis showed the presence of alkaloids, tannins, flavonoids, phenolic acids, essential oil, vitamins and others. Borage is cultivated all over the world and used in traditional medicine as a demulcent, diuretic, emollient, tonic, expectorant, for the treatment of coughs, inflammation and swelling, and other diseases. In herbal medicine, Borage seed oil (BSO) has been utilized for many progres­sive illnesse

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Publication Date
Sun Feb 01 2015
Journal Name
Italian Journal Of Geosciences
Characteristics of Clays Stabilized with Lime-Silica Fume Mix
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Publication Date
Fri Jan 01 2016
Journal Name
Journal Of Colloid And Interface Science
Wettability alteration of oil-wet carbonate by silica nanofluid
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Changing oil-wet surfaces toward higher water wettability is of key importance in subsurface engineering applications. This includes petroleum recovery from fractured limestone reservoirs, which are typically mixed or oil-wet, resulting in poor productivity as conventional waterflooding techniques are inefficient. A wettability change toward more water-wet would significantly improve oil displacement efficiency, and thus productivity. Another area where such a wettability shift would be highly beneficial is carbon geo-sequestration, where compressed CO2 is pumped underground for storage. It has recently been identified that more water-wet formations can store more CO2. We thus examined how silica based nanofluids can induce such a wettabil

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Publication Date
Sat Jun 01 2019
Journal Name
Geoderma
Effect of cover crop management on soil hydraulic properties
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Publication Date
Tue Feb 01 2022
Journal Name
Baghdad Science Journal
Physical Properties of Cu Doped ZnO Nanocrystiline Thin Films
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Thin films of ZnO nano crystalline doped with different concentrations (0, 6, 9, 12, and 18 )wt. % of copper were deposited on a glass substrate via pulsed laser deposition method (PLD). The properties of ZnO: Cu thin-nanofilms have been studied by absorbing UV-VIS, X-ray diffraction (XRD) and atomic force microscopes (AFM). UV-VIS spectroscopy was used to determine the type and value of the optical energy gap, while X-ray diffraction was used to examine the structure and determine the size of the crystals.  Atomic force microscopes were used to study the surface formation of precipitated materials. The UV-VIS spectroscopy was used to determine the type and value of the optical energy gap.

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Publication Date
Thu Dec 19 2024
Journal Name
Al-rafidain J Med Sci
Assessment of High Risk Pregnant Women by Fetal Echocardiography
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