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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 Apr 14 2024
Journal Name
Kufa Journal For Agricultural Sciences
Growth and production of three potato cultivars as affected by organic foliar nutrition
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Publication Date
Wed Jan 01 2020
Journal Name
International Conference Of Numerical Analysis And Applied Mathematics Icnaam 2019
Investigate of TiO2 and SnO2 as electron transport layer for perovskite solar cells
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Publication Date
Tue Jun 01 2021
Journal Name
International Journal Of Aquatic Sience
Helminths and their fish hosts as bioindicators of heavy metal pollution: A review
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Publication Date
Mon Mar 02 2026
Journal Name
Magazine Aldhakwat Albedh
The impact of atheism on the individual and society, Iraq as a model
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Atheists have spread in the modern era, so that atheism has become a bad phenomenon in the world in general and in Islamic societies in particular, so the research aims to study the individual and social effects left by atheism on the atheists themselves, and the research included multiple axes: atheism linguistically and idiomatically, atheism in the Qur’an Noble and Modern (and Contemporary) Atheism Statistics: and the reasons for atheism: Studying the phenomenon of atheism in Iraq as a model, then studying the effects of atheism: on the individual first, then atheism and its impact on society, then the conclusion, recommendations, sources and references

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Publication Date
Wed Jun 15 2016
Journal Name
Iraqi National Journal Of Chemistry
Physical and Electrical Study of Different Carbone Nanomaterials as Modifying Material for SPCE
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In this work was prepared three different types of modified screen printed carbon electrode (SPCEs) with drops casted method, the used carbone nanomaterials were the MWCNT, functionalized –MWCNT (f-MWCNT) and After several experiments were made to find an appropriate ratio to make good GOT/f-MWCNT nanocomposite, and found the suspension mixture (1:1) from GOT/f-MWCNT (f-MWCNT-GOT). The electrical and physical properties were performed with cyclic voltammeter technique, and studied the maximum current response, the effective surface area, effect of the pH value and the determination of active surface area for MWCNT-SPCE , f-MWCNT-SPCE and f-MWCNT-GOT/SPCE as (0.04 cm2), (0.119 cm2) and (0.115 cm2) respectively, the surface coverage concent

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Publication Date
Fri Feb 01 2019
Journal Name
Indian Journal Of Natural Sciences
Surface Photometry and Morphology Properties of Spiral Galaxies: NGC4725, NGC4639 as Case Study
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In this study, two active galaxies (NGC4725, NGC4639) have been chosen to study their morphological and photometric properties, by using the IRAF ISOPHOTE ELLIPS task with griz-filters. Observations are obtained from the Sloan Digital Sky Survey (SDSS) which reaches now to the DATA Release (DR14). The data reduction of all images (bias and flat field) has been done by SDSS Pipeline. The surface photometric investigation was performed like the magnitude. Together with isophotal contour maps, surface brightness profiles and a bulge/disk decomposition of the images of the galaxies, although the disk position angle, ellipticity, and inclination of the galaxies have been done. Also, the color of galaxies was studied, where chromatic distribution

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Publication Date
Wed Apr 07 2021
Journal Name
Egyptian Journal Of Chemistry
Copolymers of Castor and Corn Oils with Lauryl Methacrylate as Green Lubricating Additives
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During the last few years, the greener additives prepared from bio-raw materials with low-cost and multifunctional applications have attracted considerable attention in the field of lubricant industry. In the present work, copolymers derived from sunflower and linseed oils with decyl methacrylate were synthesized by a thermal method using benzoyl peroxide (BPO) as a radical initiator. Direct polymerization of fatty acid double bonds in the presence of a free radical initiator results in the development of environmentally friendly copolymeric additives (Co-1 and Co-2). Fourier Transform Infrared (FTIR) and Proton Nuclear Magnetic Resonance (1H-NMR) were used to characterize the resulting copolymers. Thermal decomposition of copolymers was de

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Publication Date
Wed Aug 31 2022
Journal Name
Al-kindy College Medical Journal
Left Flank Pain and Hydronephrosis as the Initial Presentations of Advanced Gastric Cancer
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Ureteric obstruction is rarely noted in cases of gastric cancer. Its involvement by distant metastasis from gastric adenocarcinoma without direct invasion is an exceptionally unusual occurrence. This is the story of a 58-year-old man who arrived at the emergency department with acute flank pain and fever. He was initially diagnosed with obstructive pyelonephritis after the discovery of a new onset, complete ureteric obstruction on the left side. Subsequent investigations and follow-up revealed the presence of gastric adenocarcinoma with possible ureteric metastasis bilaterally, flank pain and hydronephrosis were the first and only presentations of gastric cancer. The rarity of the condition and the unusual presentation encouraged us to r

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Publication Date
Tue Apr 25 2023
Journal Name
Journal Of Periodontal Research
Salivary E‐cadherin as a biomarker for diagnosis and predicting grade of periodontitis
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Abstract<sec><title>Objectives

To determine the abilities of salivary E‐cadherin to differentiate between periodontal health and periodontitis and to discriminate grades of periodontitis.

Background

E‐cadherin is the main protein responsible for maintaining the integrity of epithelial‐barrier function. Disintegration of this protein is one of the events associated with the destructive forms of periodontal disease leading to increase concentration of E‐cadherin in the oral biofluids.

Materials and Methods

A total of 63 patients with periodontitis (case) and 35

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Publication Date
Sun Dec 03 2017
Journal Name
Baghdad Science Journal
Preparation and Characterization of Lead Oxide Nanoparticles by Laser Ablation as Antibacterial Agent
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In this work, lead oxide nanoparticles were prepared by laser ablation of lead target immersed in deionized water by using pulsed Nd:YAG laser with laser energy 400 mJ/pulse and different laser pulses. The chemical bonding of lead oxide nps was investigated by Fourier Transform Infrared (FTIR); surface morphology and optical properties were investigated by Scanning Electron Microscope (SEM) and UV-Visible spectroscopy respectively, and the size effect of lead oxide nanoparticles was studied on its antibacterial action against two types of bacteria Gram-negitive (Escherichia coli) and Gram-positive (Staphylococcusaurus) by diffusion method. The antibacterial property results show that the antibacterial activity of the Lead oxide NPs was

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