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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
Thu Nov 01 2018
Journal Name
Iraqi National Journal Of Nursing Specialties
Impact of functional disability on lifestyle for patients with arthritis
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A descriptive study, which was using an assessment approach, was conducted for the
determination of the impact of rheumatoid arthritis and osteoarthritis patient’s functional disability
upon their life style. The study was carried out at the Rheumatology and outpatients clinics of ALKarama
Teaching Hospital, Baghdad Teaching Hospital AL-Kindey Teaching Hospital and Specialized
surgeries Teaching Hospital for the period of October 15th 2003 through May 13th 2004 in Baghdad
City. A purposive (non-probability) sample of (245) arthritis patients which was comprised (111)
rheumatoid arthritis patients and (134) osteoarthritis patients, was selected out of the early stated
settings. The questionnaire was comprised of

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Publication Date
Wed Dec 15 2021
Journal Name
Al-academy
Websites Quality Assessment of Iraqi Universities Using the WDQI Index
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The Web Design Quality Index, known as WDQI, was applied to assess the quality of websites for six Iraqi universities, namely Basra University, Mosul, Muthanna, Samarra, Dijla University College, and Al-Isra University College. The results of the index showed that the universities of Basra and Dijla University College had the highest value, at 71.07 and 70.39, respectively. Its final evaluation metric was that the website of these two universities needed a slight improvement. As for the rest of the other universities, the final values of the index ranged from 64.72-69.71. When the final values of the index are displayed on the final evaluation scale, it appears that the websites of the four universities need many improvements. The study

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Publication Date
Tue Feb 28 2017
Journal Name
Journal Of Engineering
The Impact of Urban Solid Waste Management on Urban Environment
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The growing population and the rising standard of living in cities as well as the increased commercial, industrial and agricultural activities around the world led to
massive production of waste containing different materials and one of them is the municipal solid waste (MSW), so there is a major problem facing the cities around the world about the waste, how to collect, transfer it and how to discard it. Because the accumulation of wastes, whether in the city alleys or in its squares and especially in its residential areas affect the health of their populations besides this situation will be a major indication of the deteriorating quality of life in the city, as hygiene considered a fundamental criterion for the city beauty as well

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Publication Date
Wed Jan 01 2020
Journal Name
Technologies And Materials For Renewable Energy, Environment And Sustainability: Tmrees20
Studying the effect of the annealing on Ag2Se thin film
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Publication Date
Fri Jan 01 2021
Journal Name
Latin American Journal Of Solids And Structures
Structural Behavior of Reinforced Hybrid Concrete Columns under Biaxial Loading
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Publication Date
Fri Dec 23 2022
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Plant-derived Molecules for the Treatment of Tuberculosis: A Review
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Synthetic anti-TB drugs are being used to treat tuberculosis (TB) as they are effective, however, they are accompanied by many side effects. The disease has remained largely uncured till date. The use of plant extracts or phytochemicals along with the anti-TB drugs is a very attractive strategy to make the treatment more effective as phytochemicals have no side-effects, are much less toxic than synthetic anti-TB drugs, are safe to use and most importantly, do not produce resistant strains as opposed to synthetic anti-TB drugs. Approximately 420,000 plant species have been identified globally and among them only a few have been explored for their therapeutic potential. Traditional medicine in different parts of the world has employed crud

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Publication Date
Tue Dec 01 2015
Journal Name
Journal Of Engineering
Improved Automatic Registration Adjustment of Multi-source Remote Sensing Datasets
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Registration techniques are still considered challenging tasks to remote sensing users, especially after enormous increase in the volume of remotely sensed data being acquired by an ever-growing number of earth observation sensors. This surge in use mandates the development of accurate and robust registration procedures that can handle these data with varying geometric and radiometric properties. This paper aims to develop the traditional registration scenarios to reduce discrepancies between registered datasets in two dimensions (2D) space for remote sensing images. This is achieved by designing a computer program written in Visual Basic language following two main stages: The first stage is a traditional registration p

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Publication Date
Sun Mar 01 2026
Journal Name
Journal Of Al-qalam University College
Procedural Legislative Policy for the Exercise of Preventive Public Interest
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Judicial proceedings require the judge to activate and employ his intellectual and philosophical faculties in order to arrive at a truth that is as close as possible to factual reality, which constitutes the objective sought by all procedural legislations. Among the means to which the judge resorts, within the framework of procedural laws and for the purpose of achieving the highest possible degree of procedural effectiveness in the context of civil litigation, are the concept of legal fiction and the idea of purpose (teleology). Through these mechanisms, the judge confronts certain technical difficulties related to the drafting of some procedural rules, as well as practical difficulties associated with the application of the provisions of

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Publication Date
Tue Dec 01 2015
Journal Name
Journal Of Engineering
Aeroelastic Flutter of Subsonic Aircraft Wing Section with Control Surface
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Aeroelastic flutter in aircraft mechanisms is unavoidable, essentially in the wing and control surface. In this work a three degree-of-freedom aeroelastic wing section with trailing edge flap is modeled numerically and theoretically. FLUENT code based on the steady finite volume is used for the prediction of the steady aerodynamic characteristics (lift, drag, pitching moment, velocity, and pressure distribution) as well as the Duhamel formulation is used to model the aerodynamic loads theoretically. The system response (pitch, flap pitch and plunge) was determined by integration the governing equations using MATLAB with a standard Runge–Kutta algorithm in conjunction with Henon’s method. The results are compared with

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Publication Date
Tue Jun 30 2020
Journal Name
Journal Of Economics And Administrative Sciences
The Impact of Merger strategy on human resources management practices
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The current research aims to test the impact of the strategy of merger (as an explanatory variable) in human resources management practices (as a response variable), and the importance of the subject being an important topic that mimics the Iraqi environment, where has seen many mergers that have not been addressed by former researchers in the field. In addition, the future prospects carry many mergers, and the problem of research was the lack of understanding among departments in how to manage the integration and deal with it, on the basis of scientific which reflected negatively on the practices of human resources management, and the research was based on two main hypotheses Six sub-hypotheses emerge to explore the correlation

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