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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
Tue Dec 10 2019
Journal Name
London Metropolitan University
Speech intelligibility: a study of Iraqi EFL learners’ accented English
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MR Younus…, 2020 - Cited by 2

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Publication Date
Wed Dec 15 2021
Journal Name
Abstract And Applied Analysis
Dynamical Behaviors of a Fractional-Order Three Dimensional Prey-Predator Model
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In this paper, the dynamical behavior of a three-dimensional fractional-order prey-predator model is investigated with Holling type III functional response and constant rate harvesting. It is assumed that the middle predator species consumes only the prey species, and the top predator species consumes only the middle predator species. We also prove the boundedness, the non-negativity, the uniqueness, and the existence of the solutions of the proposed model. Then, all possible equilibria are determined, and the dynamical behaviors of the proposed model around the equilibrium points are investigated. Finally, numerical simulations results are presented to confirm the theoretical results and to give a better understanding of the dynami

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Publication Date
Sun Dec 06 2015
Journal Name
Baghdad Science Journal
A new species of Solanum L.(Solanaceae) from Baghdad city Iraq
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Solanum americanum is a new annual shrubby plant seen recently in fields and gardens of Baghdad city. A new species is described and illustrated, inhabit wet or semi dry places and have consequently a mesophytic habit. A detailed morphological study of the stems, leaves, Inflorescence, flower, male and female reproductive organs and fruits has been done, revealed several interesting taxonomic characteristics, which have not previously been studied in Iraq. Also, anatomical studies reveals constant taxonomical characteristics such as the presence of anthocayanine in outer row of epidermis, distinct chlorenchyma in whole cortex, the wide pith of stems, and presence of distinct mesophyll that differentiated into palisade layer and spongy laye

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Crossref
Publication Date
Tue Aug 01 2017
Journal Name
Catalysis Science & Technology
Decomposition of selected chlorinated volatile organic compounds by ceria (CeO 2)
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Chlorinated volatile organic compounds (CVOCs) are toxic chemical entities emitted invariably from stationary thermal operations when a trace of chlorine is present. Replacing the high-temperature destruction operations of these compounds with catalytic oxidation has led to the formulation of various potent metal oxides catalysts; among them are ceria-based materials. Guided by recent experimental measurements, this study theoretically investigates the initial steps operating in the interactions of ceria surface CeO2(111) with three CVOC model compounds, namely chloroethene (CE), chloroethane (CA) and chlorobenzene (CB). We find that, the CeO2(111) surface mediates fission of the carbon–chlorine bonds in the CE, CA and CB molecules via mo

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Publication Date
Sun Jul 31 2022
Journal Name
International Review Of Civil Engineering (irece)
Bearing Capacity Factor of Shallow Foundation on Reinforced Sloped Clayey Soil
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The placement of buildings and structures on/or adjacent to slopes is possible, but this poses a danger to the structure due to failures that occur in slopes. Therefore, a solution or improvement should be determined for these issues of the collapse of the structure as a result of the failure of the slopes. A laboratory model has been built to test the impact of some variables on the bearing capacity factor. The variables include the magnitude of static axial load applied at the center of footing, the depth of embedment, the spacing between geogrid reinforcement layer and the numbering of the geogrid sheet under the footing, the inclination angle of slope clayey soil (β), the spacing between the footing's edge and the slope's end (b/H). Th

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Crossref
Publication Date
Mon Oct 06 2014
Journal Name
Journal Of Educational And Psychological Researches
The Effect of the Problem Based Learning on EFL Learners’ Achievement
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The present study discusses the problem based learning in Iraqi classroom. This method aims to involve all learners in collaborative activities and it is learner-centered method. To fulfill the aims and verify the hypothesis which reads as follow” It is hypothesized that there is no statistically significant differences between the achievements of Experimental group and control group”. Thirty learners are selected to be the sample of present study.Mann-Whitney Test for two independent samples is used to analysis the results. The analysis shows that experimental group’s members who are taught according to problem based learning gets higher scores than the control group’s members who are taught according to traditional method. This

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Publication Date
Mon Dec 03 2018
Journal Name
Journal Of Engineering
Comparative Analysis of Various Multicarrier Modulation Techniques for Different Multilevel Converters
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The applications of Multilevel Converter (MLC) are increased because of the huge demand for clean power; especially these types of converters are compatible with the renewable energy sources. In addition, these new types of converters have the capability of high voltage and high power operation. A Nine-level converter in three modes of implementation; Diode Clamped-MLC (DC-MLC), Capacitor Clamped-MLC (CC-MLC), and the Modular Structured-MLC (MS-MLC) are analyzed and simulated in this paper. Various types of Multicarrier Modulation Techniques (MMTs) (Level shifted (LS), and Phase shifted (PS)) are used for operating the proposed Nine level - MLCs. Matlab/Simulink environment is used for the simulation, extracting, and ana

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Publication Date
Sun Dec 31 2000
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Production of Low Sulfur Fuel Oil from Different Iraqi Residues Crudes
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Publication Date
Mon Jul 10 2023
Journal Name
Journal Of Engineering
Forward Osmosis Process for the Treatment of Wastewater from Textile Industries
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This paper was aimed to study the efficiency of forward osmosis (FO) process as a new application for the treatment of wastewater from textile effluent and the factors affecting the performance of forward osmosis process.
The draw solutions used were magnesium chloride (MgCl2), and aluminum sulphate (Al2 ( SO4)3 .18 H2O), and the feed solutions used were reactive red, and disperse blue dyes.
Experimental work were includes operating the forward osmosis process using thin film composite (TFC) membrane as flat sheet for different draw solutions and feed solutions. The operating parameters studied were : draw solutions concentration (10 – 90 g/l), feed solutions concentration (5 – 30 mg/l), draw solutions flow rate (10 – 50 l/hr

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Publication Date
Wed Jun 03 2020
Journal Name
Political Sciences Journal
The Political Intellectual Structures of open society according Karl Popper's Thought
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This research is trying to study the Intellectual political structures of the Open Society according to British Thinker –with Austrian origin- Karl Popper (1902-1994). In First Axe we dealt with the context of Open and Closed society in the Popper's thought. While in the Second Axe we studied the Utopian and graduated Engineering. Finally in the third Axe  for the Rationalism, Freedom, Individualism, and the Democracy of Equality. 

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