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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.

Scopus Clarivate Crossref
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Publication Date
Mon Jun 30 2014
Journal Name
Al-kindy College Medical Journal
Evaluation of Serum RANKL Level in Acute Coronary Syndrome
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Background: Acute coronary syndrome (ACS) is a common disease, and a major determinant of morbidity and mortality in all races. The pleiotropic effects of the receptor activator of nuclear factor-kappa B ligand (RANKL) such as modulation of cell survival, mineralization and inflammation, make it an interesting candidate mediator in the progression and destabilization of atherosclerotic lesions.Objectives: This study was performed to investigate the role of RANKL in the pathogenesis of ACS.Methods: The levels of RANKL were measured by ELISA method in sera of 60 ACS patients, 31 patients with unstable angina (UA) and 29 patients with myocardial infarction (MI) in comparison with 20 apparently healthy controls.Results: Current data indicate

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Publication Date
Wed Dec 12 2018
Journal Name
Iraqi National Journal Of Nursing Specialties
Evaluation of Youth's Health Risk Behaviors in Baghdad City
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Objective(s): To evaluate youth's health risk behaviors in Baghdad City and to determine the relationship between such behaviors and the youth's demographic characteristics of age, gender and grade. Methodology: A descriptive study, using the evaluation approach, is carried out to evaluate youth's health risk behaviors in Baghdad City for the period of January 26th 2016 to May 20th 2016. A non-probability "purposive" sample of (160) University students is selected for the purpose of the study from four groups of colleges (medical, engineering, sciences, and education) and it is equally distributed of

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Publication Date
Sun Sep 01 2019
Journal Name
Journal Of Physics: Conference Series
Evaluation of Nuclear safety procedures in some Iraqi universities
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Scopus Crossref
Publication Date
Fri Dec 14 2018
Journal Name
Iraqi National Journal Of Nursing Specialties
Evaluation of Personal Digital Assistant Acceptance in Nursing Education
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Objective:To measure the acceptance level of the Personal Digital Assistance (PDA)’suse among nursing students as a tool of education in the Kingdom of Saudi Arabia. Methodology: Eighty-nine nursing students participated in this cross-sectional descriptive study by completing a questionnaire based on the Technology Acceptance Model (TAM) by Davis. Two dimensions were explored and evaluated; (1) the applicability of the TAM model in assessing this technology; and (2) the overall percentage of students’ agreement on the different TAM variables. Results: This study presented significant positive influence bet

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Publication Date
Thu Apr 20 2023
Journal Name
Maaen Journal For Medical Sciences
Evaluation of heated cure acrylic immersed in ozonated water
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Background: Denture cleansing is an important step that can prevent the spread of infection and improve a patient's health, the durability of the dentures, and the overall quality of life; therefore, it is necessary to choose a suitable cleanser that, in addition to being effective, does not have an unfavorable effect on the qualities of the denture base resin itself when used for an extended period. Aim: This research aims to assess the effects of ozonated water on the surface roughness and hardness of heat-cured acrylic resin by immersion technique. Materials: Sixty bars shapemade of heat-cured acrylicweremanufactured.Thirty samples for every test, including: (surface hardness and surface roughness). Then, these samples were divided into

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Crossref
Publication Date
Sun Nov 26 2017
Journal Name
Journal Of Engineering
Compression Index and Compression Ratio Prediction by Artificial Neural Networks
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Information about soil consolidation is essential in geotechnical design. Because of the time and expense involved in performing consolidation tests, equations are required to estimate compression index from soil index properties. Although many empirical equations concerning soil properties have been proposed, such equations may not be appropriate for local situations. The aim of this study is to investigate the consolidation and physical properties of the cohesive soil. Artificial Neural Network (ANN) has been adapted in this investigation to predict the compression index and compression ratio using basic index properties. One hundred and ninety five consolidation results for soils tested at different construction sites

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Publication Date
Sun Feb 10 2019
Journal Name
Journal Of The College Of Education For Women
Woman’s Identity Crisis in the Clash of Cultures: A Study of Betool Khedairi’s Novel: A Sky So close
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This paper is an attempt to clarify the impact of Postcolonialism, one of the most
challenging fields of study that has emerged in recent years, on representations of women in
once-colonised countries and in Western locations. It discusses the influence of cultural
differences on the status and identity of a woman who experience ‗multiculturalism‘. The
study is an analytical reading of a contemporary novel written by the Iraqi writer Betool Al-
Kudairi. The emphasis lies on the clash between two different cultures and traditions
represented by the British mother and the Iraqi father and its effect on the life and identity of
the protagonist. The main focus is on idea of ‗hybrid identity‘ and the absence of th

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Publication Date
Mon Jun 25 2018
Journal Name
International Journal Of Pharmaceutical Quality Assurance
Synthesize of New Ibuprofen and Naproxen Sulphonamide Conjugate with Anti-Inflammatory Study and Molecular Docking Study
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Non-steroidal anti-inflammatory drugs (NSAIDs) contain free –COOH which thought to be responsible for the GI irritation associated with all traditional NSAIDs. The esterification of this group is one of an approach to ultimate aim for reduce the gastric irritation; so in this study we synthesized and preliminarily evaluated new ester compounds as new analogues with expected selectivity toward COX-2 enzyme. Synthetic procedures have been successfully developed for the generation of the target compounds (III a and b). The synthetic approach involved multi-steps procedures which include: Synthesis of 4-hydroxy benzene sulphonamide ( I b ), synthesis of Naproxen and Ibuprofen acyl chloride and then reacting them with 4-hydroxy benzene sulphon

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Scopus (8)
Scopus
Publication Date
Thu Dec 01 2011
Journal Name
Journal Of Economics And Administrative Sciences
marked as licensing oil and its role in future oil industry in Iraq
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Iraq's oil industry  has been passed  in different periods , began with domination  of  Western companies to invest in Iraqi oil at twenties of the last century ,  through the process of nationalization of the shares of those companies ,  beginning of the seventies , and ending with the new policies adopted by the government recently, which was contracting with international companies to develop the oil industry , because of what the outcome of the oil industry from a decline in artistic and  physical ability as a result to the  conditions of war and embargo imposed on Iraq before 2003.

The Iraqi government has introduced licensing of a contract to

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Crossref
Publication Date
Sun Dec 30 2012
Journal Name
Al-kindy College Medical Journal
Evaluation of Fludarabine, and granulocyte colony stimulating factor in treatment of efractory/Relapsed Acute Leukemias in adult Iraqi patients
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Background: Refractory/relapsed acute leukemia has always been a challenging problem for hematologist. Over the past decade emphasis has been made in the development of regimens containing fludarabine, combined with cytosine arabinoside for the treatment of refractory/relapsed acute leukemias. The aim of this study is to evaluate the efficacy and toxicity of the combination of fludarabine, high dose cytarabine, and granulocyte colony stimulating factor in refractory relapsed cases of acute leukaemia,
Methods: a prospective study is being conducted at the national center of hematology and hematology unit /Baghdad teaching hospital from July 2008 to July 2010.Twenty Patients with refractory/relapsed acute leukemia were treated with flud

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