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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
Sat Jan 01 2011
Journal Name
Journal Of Baghdad College Of Dentistry
Assessment of the accuracy of a fifth generation apex locator (in vitro study)
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Background: The use of electronic apex locators for working length determination eliminates many of the problems associated with the radiographic measurements (interference of anatomical structures, errors in projection such as elongation or shortening, and lack of three-dimensional representation). Its most important advantage over radiography is that it measures the length of the root canal to the apical constriction, not to the radiographic apex. The aim of this study was to assess the accuracy of a new fifth generation apex locator (Joypex 5) in recording the apical constriction and comparing it with a third generation apex locator (Root ZX) in vitro. Materials and method: Twenty four single-rooted sound human premolars, extracted for t

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Publication Date
Sun Sep 07 2014
Journal Name
Baghdad Science Journal
Analysis of Fatty Acid Composition in the Seed and flower oil of Syrian Ligustrun Lucidum and olive oil
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The fatty acid composition in the seed and flower of Ligustrun lucidum and olive oil was studied by Gas Chromatography. Results showed that the main components of seed oil were Palmitic (C16:0) 5,893% ,Palmitolic acid (C16:1)0,398%, Steaeic (C18:0)2,911% ,Oleic (C18:1)74,984%,Linoleic (C18:2) 12,959%,and Linolenic (C18:3) 0,997%. The proportion of unsaturated fatty acid was above 89,338%, so the seed oil of L. lucidum ait belonged to unsaturated oil which possessed promising application. The components of flower oil were Palmitic (C16:0) 65,674% ,Palmitolic acid (C16:1)6,516%, Steaeic (C18:0)2,641% ,Oleic (C18:1)14,707%,Linoleic (C18:2) 3,113%,and Linolenic (C18:3) 2,70%. The proportion of unsaturated fatty acid and saturated fatty acid wa

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Publication Date
Mon Aug 22 2022
Journal Name
World Bulletin Of Management And Law
THE IMPACT OF OUTSOURCING OF HUMAN RESOURCE ACTIVITIES ON ORGANIZATIONAL WINNING(FIELD RESEARCH IN A SAMPLE OF PREMIUM CLASS HOTELS -IN IRAQ)
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The aim of the research is to test the effect of outsourcing human resources activities (independent variable) with its dimensions (outsourcing of staffing, outsourcing of training and development, outsourcing of wages and compensation, outsourcing of human resources information systems) on organizational winning (dependent variable) with its dimensions (the culture of winning, successful organizational change, continuous improvement, and adoption of risk). The research problem was the questions posed by the researcher, the most important of which is the extent to which the research sample realizes the importance of applying outsourcing to human resources activities and its role in organizational vi

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Publication Date
Sun Jan 21 2018
Journal Name
Drug Invention Today
Preparation and evaluation of lornoxicam in situ gelling liquid suppository
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Publication Date
Sun Jul 17 2022
Journal Name
Pharmacy Education
Students' experience and evaluation of community pharmacy internship in Iraq
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Background: Pharmacy internship programmes are driven by most developed countries to outweigh the ongoing growth in the pharmacy career which encourages pharmacists to play a significant role as healthcare providers.    Objectives: This study examines pharmacy students' perception, satisfaction, challenges, and limitations with the internship curriculum.    Method: A cross-sectional study was conducted using an online survey with different elements to examine students' perceptions of various aspects.    Result: Most students reported a positive impression regarding their internships, however, they were less satisfied with the allowance for filling prescriptions and compounding also, the college's follow-up was inadequate. F

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Publication Date
Thu Jan 01 2026
Journal Name
Journal Of The Iranian Chemical Society
Synthesis, characterization and evaluating their activity as antioxidants and anticancer of new metal ion complexes with new Azo dye
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This paper presents a new Azo dye that was prepared from the reaction of the Benzene-1,2-diamine and 1-(2,4,6-Trihydroxy-phenyl)-ethanone, Azo dye was used to prepare a new series of complexes with general formula: [Co2(H4L) Cl2(H2O)4] and [M2(H4L)Cl4(H2O)2] (M= Cr+3, Fe+3,Rh+3 and Ru+3). The prepared materials were different measurements including to infrared, ultraviolet-visible, and mass spectrometry, as well as thermo gravimetric analysis, differential calorimetry, and elemental analysis. Conductivity, magnetic susceptibility, metal content, and chlorine content of the complexes were also assessed. The complexes prepared from the dye were used to determine their ability to inhibit free radicals by measuring their antioxidant capacity us

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Publication Date
Thu Jan 01 2026
Journal Name
Journal Of The Iranian Chemical Society
Synthesis, characterization and evaluating their activity as antioxidants and anticancer of new metal ion complexes with new Azo dye
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Publication Date
Tue Jan 29 2019
Journal Name
Journal Of The College Of Education For Women
Derivatives in reading behind bin Hisham al-Bazzar Morphological study
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One of the main criteria taken by the reader in the correct reading of a statement is the standard morphological, Vabv Eetmisah from the rest of science that examines the word andchanges therein lead to new meanings, which is the rule months in Morphology, every increase in construction lead to an increase in meaning.
Who took behind with the likes of ten readers Morphology a way to show the most rightly reading, to perform the desired effect, it has committed as committed behind bin Hisham statement argument morphological under which the clear sense of the formula of distinguished from Matheladtha of formulas feature to perform their intended meaning. And here that God Almighty was meant to each formula is contained in verse without

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Publication Date
Fri Jan 01 2021
Journal Name
Aip Conference Proceedings
Plasma levels and diagnostic utility of MMP-2 and TIMP-2 in the diagnosis of Iraqi women with breast tumor: A comparative study with Ca 15-3
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Publication Date
Fri Jan 01 2021
Journal Name
Aip Conference Proceedings
Plasma levels and diagnostic utility of MMP-2 and TIMP-2 in the diagnosis of Iraqi women with breast tumor: A comparative study with Ca 15-3
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