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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
Mon Mar 30 2009
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Purification of Zinc Oxide Using Direct Thermal Process by Petroleum Coke
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The present investigation is concerned for the purification of impure zinc oxide (80-85 wt %) by using petroleum coke
(carbon content is 76 wt %) as reducing agent for the impure zinc oxide to provide pure zinc vapor, which will be
oxidized later by air to the pure zinc oxide.
The operating conditions of the reaction were studied in detail which are, reaction time within the range (10 to 30 min),
reaction temperature (900 to 1100 oC), air flow rate (0.2 to 1 l/min) and weight percentage of the reducing agent
(petroleum coke) in the feed (14 to 30 wt %).
The best operating conditions were (30 min) for the reaction time, (1100 oC) for the reaction temperature, (1 l/min) for
the air flow rate, and (30 wt %) of reducing

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Publication Date
Tue Mar 31 2015
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Extraction of Aromatic Hydrocarbons from Lube Oil Using Different Co-Solvent
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An investigation was conducted effect of addition co- solvent on solvent extraction process for two types of a lubricating oil fraction (spindle) and (SAE-30) obtained from vacuum distillation unit of lube oil plant of Daura Refinery. In this study two types of co-solvents ( formamide and N-methyl, 2, pyrrolidone) were blended with furfural to extract aromatic hydrocarbons which are the undesirable materials in raw lubricating oil, in order to improve the viscosity index, viscosity and yield of produced lubricating oil. The studied operating condition are extraction temperature range from 70 to 110 °C for formamide and 80 to 120 °C for N-methyl, 2, pyrrolidone, solvent to oil ratio range from 1:1 to 2:1 (wt./wt.) for furfural with form

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Publication Date
Wed Feb 27 2019
Journal Name
Political Sciences Journal
Effects of Neighboring Countries on the Iraqi Parliament Performance after 2003
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Publication Date
Wed Oct 18 2023
Journal Name
Iraqi National Journal Of Nursing Specialties
The Impact of Nutrition Education Program upon Pregnant Mothers’ Nutritional Knowledge
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Objective: Determine the effectiveness of the Nutrition Education Program upon the pregnant mothers'
nutritional knowledge.
Methodology: ٨ quazi-experimental study was carried out to determine the effectiveness of the nutrition
education program upon the pregnant mother's nutritional knowledge. A non-probability "purposive sample" of
(60) pregnant mother was selected from Al-bayaa' Primary Health Care Center in Baghdad City. These mothers
were divided into two equal groups; study group and control group. A questionnaire was developed as a tool of
data collection for the purpose of the study. A pilot study and follow-up was carried out to test the reliability and
validity of the questionnaire for the period of Octobe

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Publication Date
Sat Jan 01 2022
Journal Name
Journal Of The Mechanical Behavior Of Materials
Identifying the selection criteria of design consultant for Iraqi construction projects
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Abstract<p>The quality and cost of constructed buildings are heavily influenced by the performance of design/auditing consultants. Thus, selecting the right design consultant and design auditing consultants is of utmost importance and not an easy task for any construction client. so, the client should specify the efficiency criteria and assess the performance levels of the design and design auditing consultant firm. The study aims to identify the selection criteria of the design consultant in construction projects and also identify the selection criteria of the design auditing consultant for the construction projects by using the Delphi survey with applying the principal components analysis (PCA</p> ... Show More
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Publication Date
Wed Nov 04 2020
Journal Name
Advances In Mobility-as-a-service Systems
Community Participation Towards Sustainability Enhancement of Transportation Sector for Baghdad City
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Publication Date
Fri Jan 01 2021
Journal Name
Tigris And Euphrates Rivers: Their Environment From Headwaters To Mouth
Ornamental Fishes: A Looming Danger for Inland Fish Diversity of Iraq
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Publication Date
Sun May 28 2017
Journal Name
Ibn Al-haitham Journal For Pure And Applied Science
On-Line Navigational Problem of a Mobile Robot Using Genetic Algorithm
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Publication Date
Thu Oct 01 2020
Journal Name
Biochemical And Cellular Archives
QUANTITATIVE ANALYSIS OF SOME AROMATIC AMINO ACIDS BY SPECTROPHOTOMETRIC MATHEMATICAL DERIVATIZATION
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A simple UV spectrophotometric differential derivatization method was performed for the simultaneous quantification of three aromatic amino acids of tryptophan, the polar tyrosine and phenylalanine TRP, TYR and PHE respectively. The avoidance of the time and reagents consuming steps of sample preparation or analyze separation from its bulk of interferences made the approach environmentally benign, sustainable and green. The linear calibration curves of differential second derivative were built at the optimum wavelength for each analyze (218.9, 236.1 and 222.5 nm) for PHE, TRP and TYR respectively. Quantification for each analyze was in the concentration range of (1.0– 45, 0.1–20.0 and 1.0– 50.0 μg/ml) at replicates of (n=3) with a re

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Publication Date
Wed Sep 16 2015
Journal Name
Journal Of The College Of Basic Education
Formation of self-assembled polymeric complexes with bridged azido-dicarboxylato ligands
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In this publication, several six coordinate bridged-polymeric metal complexes are reported. The reaction of 4,4`-dipyridine with ethyl chloroacetate in mole ratio of 1:2 gave the multidentate carboxylate ligand bis(N-carboxylatomethyl)-4,4`-dipyridinium). The reaction of the ligand with metal chloride and sodium azide resulted in the formation of the required polymeric complexes. Upon complex formation, the carboxylato ligand behaves as a neutral multidantate species. The mode of bonding and overall geometry of the complexes were determined through physicochemical and spectroscopic methods. These studies revealed octahedral geometry about metal centres and complexes of the general formula [Cr2(L)(N3)4]Cl2.H2O, Na2[Ag2(L)(N3)4].H2O and [M2(L

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