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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
Mon Jul 25 2022
Journal Name
International Journal Of Health Sciences
Ca242 as a potential prognostic marker in colorectal cancer Iraqi patients
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Background: Colorectal cancer is the third most common cancer-related mortality worldwide, and its prevalence is increasing among many nations.  Aim of the study: Investigate the predictive value of carbohydrate antigen 242 (CA242) in comparison to the CEA biomarker and to estimate the significance of CA242 as prognosis maker in colorectal cancer patients. Methods: a case-control study with a total of 150 individuals, 100 patients (59 males, 41 females) and 50 healthy controls (26 males, 24 females). using an enzyme-linked immunosorbent (ELISA) to determine the serum levels of CA242 and CEA. The study was carried out at the gastroenterology consultation clinic of the oncology teaching hospital between November 2020 and February

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Publication Date
Thu Oct 01 2020
Journal Name
Journal Of Legal Sciences
Judicial Tools in Developing Civil Law Rules – France as a Model
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Despite the principle of separation of powers brought by the French Revolution, which entrusted the task of drafting legislation and its amendment to the legislative authority and the task of settling disputes and settling them in the judiciary. However, since that date, the French judiciary has played a major role in the development of French civil law (In spite of all the economic and social developments that have taken place in French society throughout these years) since its promulgation until February of 2016, the date of the Legislative Decree No. 131 of the year 2016 A modification is the largest in the history of the French Civil Code (which was the judicial precedents in which a significant impact), was assisted by the French judic

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Publication Date
Fri Dec 15 2023
Journal Name
Al-academy
Design contexts in interior space design (sewing workshops as a model)
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The topic of context is one of the important topics, which was mentioned as a concept in several fields and different fields, and there were many points of view that defined that concept.
He specified the title of the research (design contexts in the design of the interior space), as the research sought to identify the concept of context in the interior design of the spaces of sewing workshops. The research was divided into four chapters:
The first chapter, which consists of the methodological framework, the problem of research and the need for it, the importance of research, the goal and limits of research for sewing workshops for vocational schools from (2020-2021).
The second chapter: consists of previous studies and the theo

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Publication Date
Sun Dec 31 2023
Journal Name
Revue Académique De La Recherche Juridique
Humanizing Legal Rules (The Winter Truce in France as a Model)
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Since the law is the tool for implementing the state’s public policies, it is natural that its provisions (or at least some of them) seek to preserve human dignity as the source on which all rights and freedoms are based. One of the examples of humanizing the provisions of the law in France is what is known as the winter truce. What is this truce, what are the justifications for granting it, what is its historical origin, how did the legislative treatment of it develop, what are the similarities and differences between it and other legal periods included in French law, what is the scope of its application, and what are the effects resulting from it. These questions and others are what we will try to answer through this research.

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Publication Date
Wed Jul 13 2022
Journal Name
International Journal Of Health Sciences
Study of the reliability of serum vascular endothelial growth factor and its soluble receptor as markers of diabetic nephropathy in type 2 diabetes patients
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The levels of circulating angiogenic and anti-angiogenic factors, namely vascular endothelial growth factor–A (VEGF-A) and soluble vascular endothelial growth factor receptor-1 (sVEGFR-1), have been linked to the development of renal dysfunction due to the proliferation of microvasculature within the kidneys of type 2 diabetic (T2DM) patients. The study aims to scrutinize serum levels of VEGF and sVEGFR-1 in a sample of Iraqi diabetic nephropathy patients to support their reliability as markers for the prediction of nephropathy in type 2 diabetes mellitus patients as well as to assess the ACE inhibitor’s effect on the levels of these two markers. Method: The ninety participants of this case-control study were split into three gr

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Publication Date
Wed Jun 13 2018
Journal Name
Rasayan Journal Of Chemistry
Novel Thermodynamic Properties of Binary Mixtures of Tetrahydrofurfuryl Alcohol wiyh some Alcohols At 298.15 K
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Publication Date
Mon Jan 01 2018
Journal Name
Rasayan Journal Of Chemistry
NOVEL THERMODYNAMIC PROPERTIES OF BINARY MIXTURES OF TETRAHYDROFURFURYL ALCOHOL WITH SOME ALCOHOLS AT 298.15 K
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Publication Date
Tue Dec 05 2023
Journal Name
Baghdad Science Journal
A Novel Water Quality Index for Iraqi Surface Water
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The study aims to build a water quality index that fits the Iraqi aquatic systems and reflects the environmental reality of Iraqi water. The developed Iraqi Water Quality Index (IQWQI) includes physical and chemical components. To build the IQWQI, Delphi method was used to communicate with local and global experts in water quality indices for their opinion regarding the best and most important parameter we can use in building the index and the established weight of each parameter. From the data obtained in this study, 70% were used for building the model and 30% for evaluating the model. Multiple scenarios were applied to the model inputs to study the effects of increasing parameters. The model was built 4 by 4 until it reached 17 parame

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Publication Date
Tue Mar 28 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Guggulusome - A Novel Vesicular Carriers for Enhanced Transdermal Delivery
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The present work describes guggul as a novel carrier for some anti-inflammatory drugs. Guggulusomes containing different concentration of guggul with aceclofenac were prepared by sonication method and characterized for vesicle shape, size, size-distribution, pH, viscosity, spread ability, homogeneity, and accelerated stability in-vitro drug permeation through mouse skin. The vesicles exhibited an entrapment efficiency of 93.2 ± 12%, vesicle size of 0.769 ± 3μm and a zeta potential of - 6.21mV. In vitro drug release was analyzed using Franz’s diffusion cells. The cumulative release of the guggulusomes gel (G2) was 75.8% in 18 hrs, which is greater than that all the gel formulation. The stability profile of prepare

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Publication Date
Fri Sep 30 2022
Journal Name
Iraqi Journal Of Science
A Class of Harmonic Multivalent Functions for Higher Derivatives Associated with General Linear Operator
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    The main goal of this paper is to introduce the higher derivatives multivalent harmonic function class, which is defined by the general linear operator. As a result, geometric properties such as coefficient estimation, convex combination, extreme point, distortion theorem and convolution property are obtained. Finally, we show that this class is invariant under the Bernandi-Libera-Livingston integral for harmonic functions.

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