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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
Fri Oct 30 2020
Journal Name
Journal Of Economics And Administrative Sciences
Institutional Performance Assessment using a model of the European Foundation for Quality Management (EFQM) A case study at an organization
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The study aims to use the European Excellence Model (EFQM) in assessing the institutional performance of the National Center for Administrative Development and Information Technology in order to determine the gap between the actual reality of the performance of the Center and the standards adopted in the model, in order to know the extent to which the Center seeks to achieve excellence in performance to improve the level of services provided and the adoption of methods Modern and contemporary management in the evaluation of its institutional performance.

The problem of the study was the absence of an institutional performance evaluation system at the centre whereby weaknesses (areas of improvement) and st

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Publication Date
Sun Dec 15 2019
Journal Name
Al-academy
The Effect of The Illustration Program on Fashion Design Inspired by Historical Costumes: تهاني ناصر العجاجي -هدى عبد العزيز المقرن
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This research aims to identify the role and impact of illustrations in contemporary fashion design inspired by historical costumes. Historical fashion aesthetics are adapted to design drawings. The experimental method was followed and a sample of 31 students in the department of fashion and textile design, third level were selected. Each student carried out two original historical and contemporary design. The models were executed two times: one with the usage of the program and the other without program help. The tools that were used are the program, the scale, the pre-skill test, and the post-skill test. One of the most relevant results of the research is the possibility of using historical costumes to highlight creativity and innovatio

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Publication Date
Mon Oct 01 2018
Journal Name
International Journal Of Biosciences
Detection of Escherichia coli O157 H7 isolated from infected dogs with urinary tract infections using real time - polymerase chain reaction
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Publication Date
Wed Jan 30 2019
Journal Name
Journal Of The College Of Education For Women
Japanese territorial dispute about the Soviet northern provinces )South Kuril Islands until the end of the Cold War( Historical Study
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The imposition of (state) policy on the South Kuril Islands.In the Pacific was a subject
of borders dispute between Japan and Soviet Union which appeared clearly afterthe second
Great War and during the cold war. Despite the end of the Cold War and the collapse of the
Soviet Union in 1991, this conflict has continued, thus both countries had to made a historic
and legitimate claims to demand the rights of sovereignty and ownership of four islands
occupied by the Soviet Union after World War II under the international conventions and
treaties, but these claims are proven failures through the continuation of the regional conflict.

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Publication Date
Sun Jan 01 2012
Journal Name
مجلة واسط للعلوم والطب
Study of nuclear characters to some 164, 166, 168 68 Er isotopes by using the interacting boson model IBM-1
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The aim of this study is to show the concepts of nuclear shape and the geometrical picture to the even-even nuclei of 164,166,168E isotopes in the context of the Interacting boson Model IBM-1. The energy spectra were calculated and the effective charge values (eB) of the electromagnetic transition strength were obtained and used to calculate the B(E2) values of the electromagnetic transitions and the quadrupole moment Q of 2+ -states. The Hamiltonian parameters were calculated by taking in account the properties of these nuclei. Comparison were made with the available experimental data and included in tables. The geometrical picture of these nuclei were looked at by calculating the deformation which were represented by the potentia

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Publication Date
Mon Feb 04 2019
Journal Name
Journal Of The College Of Education For Women
The Iraqi opposition press from The P.M. Yaseen Al-Hashimi second term till the death of king Ghazi ( 1935 – 1939 )
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At the beginning of 1935 theMinistry of (Yasin AL-Hashimi) was formed which was the result of the (Sulayikh)Conference .The new ministys policy was towards the authority of the one party and the exclusivity of power.The policy of (Yasin AL-Hashemi)has faced severe campaigns from the AL-Ekhaa and AL-Ahaly newspapers.The new ministry like its predecessor ministries . When it faces criticism from opposition newspapers .its shutting down newspapers and not accepting requests for them. Some opposition newspapers named Yassin AL-Hashemi (the dictator).Iraqi opposition newspapers have been neglected and deprived of press freedom although they were the main factor in educating the community and representing the public opinion of people . Lt appe

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Publication Date
Sun Jun 01 2014
Journal Name
Baghdad Science Journal
Preparation, Characterization & Biological activity for Some Iron(II) Complexes Containing Mixed Ligands (Benzilazine & Semicarbazone) & Study of Laser Effect on Them
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The research included preparation of new iron(II) complexes with mixed ligands including benzilazine(BA) and semicarbazone ligands {benzilsemicarbazone- BSCH or benzilbis(semicarba-zone)- BBSCH2 or salicylaldehydesemicarbazone- SSCH2 or benzoinsemicarbazone- B'SCH2}.by classical and microwave methods. The resulted complexes have been characterized using chemical and physical methods. The study suggested that the above ligands form ionic complexes having formulae [Fe(SCHi)(BA)(Cl)m](Cl)2-m {where SCH, BSCH, BBSCH2, SSCH¬2 or B'SCH2 ligands; m=1 or 2}. Hexacoordinated mononuclear complexes have been investigated by this study and having octahedral geometries. The effect of laser ray type visible region have been studied on solid ligands and

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Publication Date
Fri Oct 02 2026
Journal Name
Modern Sport
Determining standard levels to test the strength endurance characteristic of speed for basketball players for juniors aged under (16) years
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Publication Date
Sun Jun 30 2024
Journal Name
Anbar Journal Of Agricultural Sciences
THE GENETIC DIAGNOSIS OF THE BACTERIA ISOLATED FROM THE AGRICULTURAL SOIL SUSTAINED FARMS BY THE POLYMERASE CHAIN REACTION TECHNIQUE QPCR
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The measurements and tests of the samples conducted in the laboratories of the College of Agriculture included isolating bio-fertilizers and testing the efficiency of isolates that fix atmospheric nitrogen and solubilize phosphorous compounds. Bacteria were isolated and identified from the rhizosphere soils of different plants collected from various agricultural areas. A total of 74 bacterial isolates were obtained based on the phenotypic characteristics of the developing colonies, as well as biochemical and microscopic traits. The results of isolation and identification showed that among the 74 bacterial isolates, there were 15 isolates of A. chroococcum, 13 of Az. lipoferum, 13 of B. megaterium, 10 of P. putida, 10 of Actinomycetes, and n

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Publication Date
Fri Sep 30 2022
Journal Name
Journal Of Economics And Administrative Sciences
Choosing the best method for estimating the survival function of inverse Gompertz distribution by using Integral mean squares error (IMSE)
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In this research , we study the inverse Gompertz distribution (IG) and estimate the  survival function of the distribution , and the survival function was evaluated using three methods (the Maximum likelihood, least squares, and percentiles estimators) and choosing the best method estimation ,as it was found that the best method for estimating the survival function is the squares-least method because it has the lowest IMSE and for all sample sizes

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