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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
Wed Dec 14 2011
Journal Name
Journal Of Faculty Of Medicine Baghdad
The correlation between FEV1/ FVC with Arm span to height or chest to waist ratio as an index of pulmonary function in healthy subject.
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Abstract

Publication Date
Sun Jul 02 2023
Journal Name
Nanomedicine Research Journal
Gold and Silver Nanoparticles with Modified Chitosan /PVA : Synthesis, Study The Toxicity and Anticancer Activity
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The new novel polymers nanocomposites based modified chitosan (CS) blending with polyvinyl alcohol (PVA) and coated gold or silver nanoparticles (AuNPs), AgNPs) were synthesized from many sequence reactions as presented in (Scheme1, 2 and 3). By utilizing 1H-NMR spectroscopy, FTIR, and Field Emission Scanning electron microscope , the synthesized compounds have been identified. Molecular docking is studied, where operations are used to predict the binding status of compounds with the enzyme and to calculate the free energy (ΔG) of the compounds prepared. Also, the antibacterial activity regarding the synthesized compounds against two resistant pathogenic bacteria (G+) S. aureus and E. coli (G-) was examined in vitro compare with standard a

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Publication Date
Sun Jan 01 2017
Journal Name
Aro-the Scientific Journal Of Koya University
A Comparative Study for String Metrics and the Feasibility of Joining them as Combined Text Similarity Measures
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Publication Date
Fri Mar 15 2019
Journal Name
Al-khwarizmi Engineering Journal
Effect Use of Two Chemical Compounds Sodium Nitrate and Sodium Silicate as Corrosion Inhibitor to Steel Reinforcement
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Corrosion of steel reinforcement is one of the biggest problems facing all countries in the world like bridges in the beach area and marine constructions which lead to study these problems and apply some economical solutions. According to the high cost of repair for these constructions, were studied the effect of using kind of chemical compounds sodium nitrite(NaNO2) and sodium silicate(Na2SiO3) as corrosion inhibitors admixture for steel bars that immersed partially in electrolyte solution (water + sodium chloride in 3% conc.) (Approximately similar to the concentration of salt in sea water). The two inhibitors above added each one to the electrolyte solution at concentrations (0.5%, 1% and 2%) for both

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Publication Date
Thu Apr 01 2021
Journal Name
J Nanostruct
Effect of Sulfur and Nitrogen co-Doped Graphene Quantum Dots on Co3O4 Nanoparticles as Solar Induced Photocatalyst
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The photocatalyst process is considered the most promising method for the removal of water contamination. For excellent chemical and structural properties of Co3O4 nanoparticles, various Co3O4-based nanostructures can be applied as a photocatalyst. In this work, carbon quantum dots is prepared via an eco-friendly process and linked to Co3O4 effectively. X-ray diffraction pattern (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), UV-visible absorption spectroscopy and Fourier transform infrared spectroscopy (FT-IR). The photocatalyst process reveals that prepared nanocomposites can be degraded methylene blue under solar irradiation strongly. Results showed that methylene blue and methyl orange are degraded via

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Publication Date
Sun Jul 09 2023
Journal Name
Journal Of Engineering
Parametric Study of Active Solar Heating Using a Pebble Bed as a Thermal Collector and Storage Unit
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In this study, pebble bed as an absorber and storage material was placed in a south facing, flat plate air-type solar collector at fixed tilt angle of (45°). The effect of this material and differ- ent parameters on collector efficiency has been investigated experimentally and
theoretically. Two operation modes were employed to study the performance of the solar air heater. An inte- grated mode of continuous operation of the system during the period of (11:00 am – 3:00 pm) and non-integrated mode in which the system stored the solar energy through the day then used the stored energy during the period of (3:00 pm – 8:00 pm). The results of parametric study in case of continuous operating showed that the maximum average temperatur

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Publication Date
Mon Nov 28 2016
Journal Name
Separation Science And Technology
Using sewage sludge as a permeable reactive barrier for remediation of groundwater contaminated with lead and phenol
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Publication Date
Wed Mar 16 2022
Journal Name
Journal Of Educational And Psychological Researches
Cognitive Distortions and Time Management as Predictors of Academic Procrastination among Students from Al Aqsa Community College
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The study aimed to reveal the possibility of predicting academic procrastination through both Cognitive distortions and time management among students of Al-Aqsa Community College, as well as to reveal the level of both cognitive distortions, time management, and academic procrastination. Additionally, it aimed to identify the size of the correlation between cognitive distortions, time management, and academic procrastination. The study sample consisted of (250) students from Al-Aqsa community college students. The results of the study concluded that the mean for each level of cognitive distortions and academic procrastination is average. The mean level of time management is high. There is a statistically significant positive relationshi

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Publication Date
Sun Sep 01 2019
Journal Name
Baghdad Science Journal
A New Method for the Isolation and Purification of Trigonelline as Hydrochloride from Trigonella foenum-graecum L.
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Separation of Trigonelline, the major alkaloid in fenugreek seeds, is difficult because the extract of these seeds usually contains Trigonelline, choline, mucilage, and steroidal saponins, in addition to some other substances. This study amis to isolate the quaternary ammonium alkaloid (Trigonelline) and choline from fenugreek seeds (Trigonella-foenum graecum L.) which have similar physiochemical properties by modifying of the classical method. Seeds were defatted and then extracted with methanol. The presence of alkaloids was detected by using Mayer's and Dragendorff's reagents. In this work, trigonilline was isolated with traces of choline by subsequent processes of purification using analytical and preparative TLC techniques.

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Publication Date
Tue Dec 31 2019
Journal Name
МИР НАУКИ, КУЛЬТУРЫ, ОБРАЗОВАНИЯ
GLUTTONICO-DISCURSIVE APHORISMS, MAXIMS, SENTATIONS, PAREMIAS (PROVERBS AND SAYINGS) AS A NATIONAL SOCIO-CULTURAL CODE OF ARABOPHONES
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The article deals with glutton-discursive aphorisms, maxims, sentations, paremias (proverbs and sayings) of different peoples, which reflect their character traits and aspects of life in the family, collective, society, everyday realities, which indicates the close connection of paremias with the language en vironment. Attention is focused on the parodies used in 73% of cases and nominating personality characteristics using the socio-cultural code of arabophones. It is proved that this vocabulary as the national socio-cultural code of arabophones are used to increase the capacity of the statement, and express the emotional and aesthetic positions of a person