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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 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
Wed Jun 29 2022
Journal Name
College Of Islamic Sciences
From the flags of The Koofic Grammar: Abdullah Al-Tuaal (243A.H)
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    This research has tackled a scientific figure belongs to Koofi grammatical school. He is Abdullah Al-Tuaal who has occupied the fourth layer among the Koofi grammarians. There was a confusion between him and another Koofi grammarian from the same layer (Mohammed Bin Qaadim) in some old references. This research has clarified this confusion to affirm that they are two different grammarians.This research also tackles the scientific status of Al-Tuaal and the grammatical views that have been ascribed to him in addition to the analysis and discussion of these views. All this in the light of what has been mentioned in grammar books about the issues in which these views were stated.

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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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Publication Date
Thu Sep 01 2016
Journal Name
Journal Of Engineering
Response of Laced Reinforced Concrete One Way Slab to Repeated Loading
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Test results of nine reinforced concrete one way slab with and without lacing reinforcement are reported. The tests were designed to study the effect of the lacing reinforcement on the flexural response of one way slabs. The test parameters were considered is the lacing steel ratios of (0, 0.0025, 0.0045, and 0.0065), flexural steel ratios of (0.0025, 0.0045, and 0.0065) and span to the effective depth ratios of (11, 13, and 16). Two specimens had no lacing reinforcement and the remaining seven specimens had the lacing reinforcement. Four point bending test were carried out, one of the specimens was tested under the static load applied gradually up to failure and the other specimens were tested under repeated load (5 cyc

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Publication Date
Mon Jun 30 2003
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Liquid-Liquid Equilibria of Quaternary Systems Including Sulfonate at 293.15 K
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Publication Date
Sat Jan 10 2015
Journal Name
British Journal Of Mathematics & Computer Science
The Use of Gradient Based Features for Woven Fabric Images Classification
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Publication Date
Wed Mar 01 2017
Journal Name
Journal Of Al-nahrain University Science
Adsorption of Ciprofloxacin Hydrochloride from Aqueous Solution by Iraqi Porcelinaite Adsorbent
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Publication Date
Tue May 01 2018
Journal Name
Journal Of Physics: Conference Series
Design of Light Trapping Solar Cell System by Using Zemax Program
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Publication Date
Wed Jul 01 2020
Journal Name
Journal Of Physics: Conference Series
A New Iterative Methods For a Family of Asymptotically Severe Mappings
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Abstract<p>The aim of this paper is to introduce the concepts of asymptotically p-contractive and asymptotically severe accretive mappings. Also, we give an iterative methods (two step-three step) for finite family of asymptotically p-contractive and asymptotically severe accretive mappings to solve types of equations.</p>
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Publication Date
Sun Dec 07 2014
Journal Name
Baghdad Science Journal
Study the Changes of Thyroid Hormones Levels Following Major Urological Surgery
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This study was designed to evaluate the effect of major surgery on thyroid hormones and thyrotropin in patient undergoing major lower abdominal surgery. The study included fifty patients scheduled for elective major lower abdominal surgery, the serum levels of T3, T4 and TSH were determined one day preoperatively, intraoperative, one day postoperatively, two days postoperatively, and rT3 was determined one day preoperatively, and one day postoperatively. We observed that the levels of (T3, T4, TSH) increased significantly (P<0.05) intraoperatively, one day postoperatively the levels of T3 and T4 reduced significantly (P<0.05), while TSH reduced not significantly (P>0.05), and two days postoperatively T4 and TSH returned to increase si

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