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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 Jun 05 2023
Journal Name
Journal Of Engineering
Compressive Behavior of Fiber Reinforced Concrete Columns Rehabilitated with CFRP Warps
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Over the last few years, there has been a worldwide increase in the use of composite materials for rehabilitation of deficient reinforced concrete structures. One important application of this technology is the use of Carbon Fiber Reinforced Polymer (CFRP) jacket to provide external confinement of reinforced concrete columns. Square concrete column specimens 100×100×1000 mm with concrete
compressive strength of about 30 and 50 MPa, steel fiber volume fraction 0%, 0.5%, 0.75%, and percentage of longitudinal reinforcement 2.01%, 3.14% and 4.52% were tested until failure in previous research. In this research seven tested columns were repaired and rehabilitated using one layer of CFRP flexible wraps and tested to determine their ultim

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Publication Date
Sun Jan 01 2023
Journal Name
International Journal Of Humanities And Social Sciences/ Rimak
AN EMPIRICAL ANALYSIS OF EDUCATIONAL RESEARCH BASED ON CRITICAL DISCOURSE ANALYSIS
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APDBN Rashid, International Journal of Humanities and Social Sciences/ RIMAK, 2023

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Publication Date
Tue Feb 06 2024
Journal Name
Research Square
Bioremediation of Cellulosic Wastes by Using Orthodillo chiltoni (Vandel, 1973), Isopoda
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Terrestrial isopods play an important role in the biodegradation of many wastes which gives agreat importance in the nutrient cycles and ecosystem services , therefore this paper aims to use species Orthodillo chiltoni (Vandel, 1973) as a model organism in bioremediation of urban environment with municipal wastes, agricultural fields, parks and markets wastes. Samples of these wastes included potato peels, orange fruit leaves, thyme plant and sawdust,cardboard residues , the experiments were carried out in laboratory condition similar to the living environment of this species in terms of temperature, humidity and intensity lighting. The applied results have shown that

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Publication Date
Sun Jun 09 2024
Journal Name
2024 Ieee 52nd Photovoltaic Specialist Conference (pvsc)
Exploring the Capacitance-Voltage Response of Metal Halide Perovskite Solar Cells
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Publication Date
Sun Mar 07 2010
Journal Name
Baghdad Science Journal
Studying the biological activity of some Antimony Compounds with amino acids
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In this work four complexes of antimony were prepared ,Na[SbO(gly)2],Na[SbO(Asp)2],Na[SbO(Tyrosin)2], Na [SbO(phen alanin)2]. by reaction SbOCl with salts amino acids identifiefid these complexes by FTIR ,their conductivity was measured and also their biological activity against two types of bacteria was studied ,they were biologically active.

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Publication Date
Fri Nov 01 2019
Journal Name
International Journal Of Engineering
Structural Behavior of Axially Loaded Composite Concrete-steel Plate Shear Walls
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Publication Date
Thu Nov 29 2018
Journal Name
Iraqi Journal Of Science
Application of WDR Technique with different Wavelet Codecs for Image Compression
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FG Mohammed, HM Al-Dabbas, Iraqi journal of science, 2018 - Cited by 6

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Scopus
Publication Date
Sat Aug 01 2015
Journal Name
2015 Ieee Conference On Computational Intelligence In Bioinformatics And Computational Biology (cibcb)
Granular computing approach for the design of medical data classification systems
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Publication Date
Fri Jul 24 2026
Journal Name
Journal Of Baghdad College Of Dentistry
The effect of inhaled corticosteroid on condition oral among asthmatic children
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Background: Inhalation therapy has been employed as the mainstay of the treatment in chronic respiratory diseases such as asthma, Patients who taking asthma medication may be at risk of many health problems including oral health .The purpose of this study was to assess the local effect of ICS on oral tissue by measuring Candida albicans count colonies in saliva among12 years old asthmatic children who were collected from AL- Zahra Center Advisory for Allergy and Asthma, and compares them with non asthmatic children of the same age and gender. Material and Methods: The total sample involved sixty children of 12 years old, thirty asthmatic children who received medium dose of ICS/day (200-400 microgram/day) for 2 years and 30 non-asthmatic ch

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Publication Date
Wed Jul 01 2020
Journal Name
Iop Conf. Series: Materials Science And Engineering
Numerical Study of Specially Shaped Slender RC Columns under Compressive Load
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Abstract<p>In most Reinforced Concrete (RC) buildings, the cross-section size of rectangular columns that conventionally used in these structures is larger than the thickness of their partitions. Consequently, a part of the column is protruded out of the wall which has some architectural disadvantages. Reducing the column size by using high strength concrete will result in slender column, thus the stability problem may be occurred. The stability problem is difficult to be overcome with rectangular columns. This paper study the effectiveness of using new types of columns called Specially Shaped Reinforced Concrete (SSRC) columns. Besides, the use of SSRC columns provides many structural advantage</p> ... Show More
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