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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 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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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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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 Jan 02 2017
Journal Name
Al-academy
Structural elements of composition design for fabrics image Image footage model
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End of the twentieth century witnessed by the technological evolution Convergences between the visual arts aesthetic value and objective representation of the image in the composition of the design of the fabric of new insights and unconventional potential in atypical employment. It is through access to the designs of modern fabrics that address the employment picture footage included several scenes footage from the film, which focuses on research and analytical as a study to demonstrate the elements of the picture and the organization of its rules and how to functioning in the design of fabrics, Thus, it has identified the problem by asking the following: What are the elements of the picture footage and how the functioning of the struct

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Publication Date
Tue Jun 01 2021
Journal Name
Iop Conference Series: Earth And Environmental Science
Implementation of hierarchically porous zeolite-polymer membrane for Chromium ions removal
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Abstract<p>This work deals with the preparation of a zeolite/polymer flat sheet membrane with hierarchical porosity and ion-exchange properties. The performance of the prepared membrane was examined by the removal of chromium ions from simulated wastewater. A NaY zeolite (crystal size of 745.8 nm) was prepared by conventional hydrothermal treatment and fabricated with polyethersulfone (15% PES) in dimethylformamide (DMF) to obtain an ion-exchange ultrafiltration membrane. The permeate flux was enhanced by increasing the zeolite content within the membrane texture indicating increasing the hydrophilicity of the prepared membranes and constructing a hierarchically porous system. A membrane contain</p> ... Show More
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Publication Date
Mon Oct 09 2023
Journal Name
2023 Ieee 34th International Symposium On Software Reliability Engineering Workshops (issrew)
Semantics-Based, Automated Preparation of Exploratory Data Analysis for Complex Systems
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Publication Date
Fri Dec 31 2021
Journal Name
Political Sciences Journal
The development of Russian-Iraqi relations for the period (2011-2019)
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Receipt date: 12/28/2020 accepted date: 20/1/2021 Publication date: 12/31/2021

Creative Commons License This work is licensed under a Creative Commons Attribution 4.0 International License.

Russia has emerged as a rising and influential power in the international arena, especially with Vladimir Putin's assumption of power and his desire for the rise of Russia and the end of the "unipolarism" represented by the hegemony of the United States of

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Publication Date
Wed Apr 05 2023
Journal Name
Journal Of Engineering
Study of the Friction Stir Welding For A516 Low Carbon Steel
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The main objective of present work is to describe the feasibility of friction stir welding (FSW) for
joining of low carbon steel with dimensions (3 mm X 80 mm X 150 mm). A matrix (3×3) of welding
parameters (welding speed and tool rotational speed) was used to see influence of each parameter on
properties of welded joint .Series of (FSW) experiments were conducted using CNC milling machine
utilizing the wide range of rotational speed and transverse speed of the machine. Effect of welding
parameters on mechanical properties of weld joints were investigated using different mechanical tests
including (tensile and microhardness tests ). Micro structural change during (FSW) process was
studied and different welding zones

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Publication Date
Wed Jan 01 2014
Journal Name
Journal Of The College Of Languages (jcl)
Bağdat’tan Derlenen Halk Masallarının İncelmesi A Studay Of Popular Baghdadi Tales
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ÖZET

Bir millet veya topluluk kendi varlığını ancak kültürel değerleri ile koruyabilecek; gelecek nesillere aktarabilecek ve dünyanın diğer milletlerine tanıtabilecektir. Böylece dünya milletleri arasında ortak kültürel ve toplumsal değerler tespit edilecek ve bu ortak değerlerden hareketle insanlık hizmetine sunulabilecek çok güzel çalışmalar hazırlanabilecektir. Taşıdıkları zengin kültürel ve toplumsal değerlerinden dolayı masalların halk edebiyatı ürünlerinin şah damarı niteliğinde oldukları söylenebilir. Bu çalışmada Türk okuruna Bağdat halk masallarını tanıtmak için sahadan derlenen on masal metnine yer verilmiştir. Bağdat masal metinlerinin tip ve motif

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Publication Date
Mon Jun 01 2020
Journal Name
Journal Of The College Of Languages (jcl)
analyzethe Surface Structure of Persian Language: تجزيه ى روساختى جمله فارسى
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  The sentence is one building unit in a music that has a full  meaning which in the end takes a long silence .The sentence bases made the sentences with  intransitive verb ( non connection ) and the sentences are   made with general verb (connection ) .The sentence parts :Verbal sentence –supportive sentence , sentence without a verb .

The method of divide the sentence into these syntax  units ( face division ) or (analysis and to each of the syntax units resulted from dividing the sentence to sections made to the end the characterizes the  smaller syntax units ,the words .The method of analyze the surface structure of Persian language sentence  is exchange method.   &nbsp

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