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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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Sat Jun 10 2023
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Lasers In Medical Science
Laser ablation of asphalt and coal in different solvents an In Vitro study
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Publication Date
Mon Jan 01 2018
Journal Name
Journal Of Engineering And Applied Sciences
Estimation of concentration of radioactive elements for the Liquid Waste pool in radiochemistry laboratories in Al Tuwaitha site Baghdad-Iraq
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Publication Date
Sun Jan 01 2023
Journal Name
Reviews In Agricultural Science
Technological Advances in Soil Penetration Resistance Measurement and Prediction Algorithms
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Soil compaction is one of the most harmful elements affecting soil structure, limiting plant growth and agricultural productivity. It is crucial to assess the degree of soil penetration resistance to discover solutions to the harmful consequences of compaction. In order to obtain the appropriate value, using soil cone penetration requires time and labor-intensive measurements. Currently, satellite technologies, electronic measurement control systems, and computer software help to measure soil penetration resistance quickly and easily within the precision agriculture applications approach. The quantitative relationships between soil properties and the factors affecting their diversity contribute to digital soil mapping. Digital soil maps use

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Publication Date
Fri Apr 01 2022
Journal Name
Chemical Methodologies
Design, Synthesis of Imidazolone and Oxazepine Derivatives Bearing Imidazo (2, 1-b) Thiazole along with its Antimicrobial Activity
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A new methodology was applied to the synthesis of new imidazolones and oxyazepine derivatives containing imidazo thiazole fused rings. Starting with 5-(4-bromo phenyl) imidazo (2, 1-b) thiazole, which was synthesized using the standard procedure, the Carbaldehyed group was introduced at position 6 of 5-(4-bromo phenyl) imidazo (2, 1-b) thiazole. Then, this 6-carbaldehyed derivative was condensed with different substituted aromatic amines to afford new Schiff bases. The latter were cyclized into new oxazepine and imidazolone derivatives by using phthalic anhydride and glycine, respectively. These new derivatives were characterized by using FT-IR, 1HHNMR, and 13CNMR spectra, as well as examined (evaluated) for anti-bacterial and anti-fungal a

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Publication Date
Fri Dec 01 2023
Journal Name
Baghdad Science Journal
Determining ACE-2 Level and Some Relevant Biochemical Parameters and studying the effect of Gender in Iraqi Diabetic Patients with Glomeruli and Renal Tubules Fibrosis as Early Prediction Marker
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     Diabetic kidney disease is an illness of the glomerulus that interferes with the glomerular filtration barrier (GFB), which is worked to enable kidney to selective purification of water and solutes in addition to limiting the movement of large macromolecules such as albumin. In the glomerular endothelium, mesangial cells, foot cells, and the brush border of the proximal tubules, ACE-2 is expressed and that the kidneys represent the highest-expressing region of this enzyme. Thus, the current study aimed to evaluate ACE-2 level in this case compared to healthy condition. The study Conducted with 120 male and female ranging in age (30-65) years old. Ninety patients with type 2 diabetes subdivided into three groups on the basis of A

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Publication Date
Sun Mar 01 2026
Journal Name
Interdisciplinary Neurosurgery
Surgical outcomes and challenges in spinal cord tumor resection: a comparative study of elderly vs. young patients
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Publication Date
Sun Jul 03 2011
Journal Name
Journal Of Educational And Psychological Researches
Educational activities in the role of government nurseries and its relationship to some variables
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The skill of management educational activities gradually grow with the experience, but they differ from personal skill educator to another, because each style nanny personally and the way to work. There educator and active movement and vitality that look like happiness and clear during the implementation of the activity, and the other runs educational activities quietly, efficiently and without emotion and clear (dry, 2001: p. 274). And the stage of childhood is one of the most important stages that are based upon the future life as a whole because the man also confirmed by the School of analysis psychological is the son of his childhood and the best example to us what the Holy Prophet Muhammad (peace be upon him): (Every child i

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Publication Date
Wed Dec 18 2019
Journal Name
Baghdad Science Journal
Detection of Nutrients and Major Ions at Al Muthanna Storage Site Soil
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In the early 90s military operations and United Nations Special Commission “UNSCOM” teams have been destroyed the past Iraqi chemical program. Both operations led an extensive number of scattered remnants of contaminated areas. The quantities of hazardous materials, incomplete destructed materials, and toxic chemicals were sealed in two bunkers. Deficiency of appropriate destruction technology led to spreading the contamination around the storage site. This paper aims to introduce the environmental detection of the contamination in the storage site area using geospatial analysis technique. The environmental contamination level of nutrients and major ions such as sulphate (SO4), potassium (K), sodium (Na), magnesi

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Publication Date
Sun Jun 01 2014
Journal Name
Baghdad Science Journal
Synthesis, Characterization and Textural Analysis of Functionalized Mesoporous Silica Using Sodium Silicate as Precursor and Silicone Surfactant as Template
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Three mesoporous silica with different functional group were prepared by one-step synthesis based on the simultaneous hydrolysis and condensation of sodium silicate with organo - silane in the presence of template surfactant polydimethylsiloxane - polyethyleneoxide (PDMS - PEO). The prepared materials were characterized by Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), atomic force microscopy (AFM) and nitrogen adsorption/desorption experiments. The results indicate that the preparation of methyl and phenyl functionalized silica were successful and the mass of methyl and phenyl groups bonded to the silica structure are 15, 38 mmol per gram silica. The average diameter of the silica particles are 103.51,

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Publication Date
Sat Nov 01 2025
Journal Name
Bulletin Of The Chemical Society Of Ethiopia
SYNTHESIS, CHARACTERIZATION, THERMAL PROPERTIES, AND BIOLOGICAL EVALUATION OF AZO-TRANSITION METAL COMPLEXES
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The coupling reaction between tryptamine and 8-hydroxyquinoline led to the formation of a new azo ligand. The synthesized ligand was characterized using CHN, FT-IR, UV-Vis, and NMR spectroscopic techniques. Complexes of the ligand with VO2+, Cr3+, Mn2+, and Mo6+ ions were prepared in a (1:2) ratio, with the general formula [M(L)2]. The obtained complexes were characterized using flame atomic absorption, CHN analysis, FT-IR, and UV-Vis spectroscopy, in addition to magnetic susceptibility and conductivity measurements. The findings suggest that the ligand functions as a bidentate, with the complexes exhibiting octahedral, square planar and square pyramidal geometries. All the complexes were identified as non-electrolytes. Their antioxidant ef

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