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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
Sun Sep 01 2024
Journal Name
Baghdad Science Journal
Isolation and Identification of Flavonoid Compounds from Euphorbia Milii Plant Cultivated in Iraq and Evaluation of its Genetic Effects on Two Types of Cancer Cell Line
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يعتبر "تاج الأشواك" أو نبات شوكة المسيح، وهو من نباتات الزينة الطبية ، ينتمي إلى جنس يوفوربيا. E. milii يحتوي كميات وفيرة من المركبات الفينولية ، التربينات، الستيرويدات والقلويدات. كانت الأهداف الرئيسية لهذه الدراسة هي فحص مستخلصات الفلافونويد والنانو فلافونويد ضد نوعين من خطوط الخلايا السرطانية. تم تصنيع مركبات الفلافونويد النانوية عن طريق تفاعل مركب الكيتوسان والماليك اسد. تم تحليل مركبات الفلافونويد ال

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Publication Date
Fri Jul 01 2016
Journal Name
Journal Of Economics And Administrative Sciences
The Role of Government Controlling Standards GAO to limit Some of Negative Phenomena According to the Anti-corruption
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Abstract :

       The research aims to diagnose some of the negative phenomena
 ( Counterfiting , Pettifogging , Embezzlement ) that have been detected over the past ( 2010 – 2014 ), a fixed-term part of the national strategy for the fight against corruption launched by the Joint Council for the fight against corruption in Iraq and measuring the application of government control according to the American standard GAO standards and identifying the potential for the application of those standards gap. It has been collecting data and information of special issues of corruption reports and meeting with (42) employees and the use of a checklist has been prepared for thi

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Publication Date
Mon May 01 2017
Journal Name
Journal Of Nuclear Medicine
Capability of a novel small field of view hybrid gamma camera (HGC) for sentinel lymph node and small organ imaging
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Objectives: Small field of view gamma detection and imaging technologies for monitoring in vivo tracer uptake are rapidly expanding and being introduced for bed-side imaging and image guided surgical procedures. The Hybrid Gamma Camera (HGC) has been developed to enhance the localization of targeted radiopharmaceuticals during surgical procedures; for example in sentinel lymph node (SLN) biopsies and for bed-side imaging in procedures such as lacrimal drainage imaging and thyroid scanning. In this study, a prototype anthropomorphic head and neck phantom has been designed, constructed, and evaluated using representative modelled medical scenarios to study the capability of the HGC to detect SLNs and image small organs. Methods: An anthropom

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Publication Date
Wed Jan 30 2019
Journal Name
Journal Of The College Of Education For Women
The Difficulties which Face Public Basic School Principals in Jarash Governorate in Editing Formal Letters and Correspondence and Means of Dealing With These Problems as Perceived by Them
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This study aimed at identity baying the difficulties which face public basic school
principals in jar ash governorate in editing formal letters and correspondence and means of
debating with these problems to collect data the researchers developed a question air were
established the population of the study which represents its sample consisted of 129 principals
65 males and 64 females
The results of the study revealed that the principals face difficulties in office and file
management in preparing plans and reports and writing formal letters and answering them
saved recommendations were presented among which were organizing training sessions and
workshops to train the principals on how to dead with there problems.<

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Publication Date
Sun Dec 31 2023
Journal Name
Lark
Digital and pedagogical practices of French as a foreign language in a post-COVID-19 context (The case of the University of Baghdad)
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Publication Date
Thu Feb 01 2024
Journal Name
Baghdad Science Journal
Polyaniline Nano Films Synthesis in One Step via Chemical Oxidative Polymerization
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Polyaniline films were successfully synthesized in this study using an oxidative polymerization method at temperatures ranging from 0 to 4 ° C. Polyaniline films were deposited using a single step of chemical oxidative polymerization rather than electrochemical polymerization. The polyaniline was examined using FTIR, XRD, SEM, AFM, and Four Point Probe. This result demonstrates that polyaniline synthesized using this method has a uniform morphology, small size (17 to 40) nm, high crystallinity, and high conductivity (9.42 s/cm).

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Publication Date
Wed Dec 15 2021
Journal Name
Al-academy
The communicative education of fine arts in the COVID-19 crisis and its manifestations in the modernization of the works of the Iraqi painter "Nabil Ali as a model"
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 This study attempts to address the importance of communicative digitization in the field of various arts for the sake of continuity of shopping and aesthetic, artistic and intellectual appreciation of artistic achievements by the recipient on various places of their residence in light of the COVID 19 crisis, and to highlight the importance of the plastic arts of the Iraqi painter exclusively and how it expresses in a contemporary way the environment or life reality in Iraq in light of this crisis. With all its implications affecting the life reality from various aspects and methods of its negative and positive employment. As for the research procedures, the researcher reviewed the research methodology represented by the descriptive ana

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Publication Date
Mon Dec 30 2013
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Permeability Prediction of Un-Cored Intervals Using FZI Method and Matrix Density Grouping Method: A Case Study of Abughirab Field/Asmari FM., Iraq
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Knowledge of permeability is critical for developing an effective reservoir description. Permeability data may be calculated from well tests, cores and logs. Normally, using well log data to derive estimates of permeability is the lowest cost method. This paper will focus on the evaluation of formation permeability in un-cored intervals for Abughirab field/Asmari reservoir in Iraq from core and well log data. Hydraulic flow unit (HFU) concept is strongly related to the flow zone indicator (FZI) which is a function of the reservoir quality index (RQI). Both measures are based on porosity and permeability of cores. It is assumed that samples with similar FZI values belong to the same HFU. A generated method is also used to calculate permea

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Publication Date
Thu Aug 02 2018
Journal Name
Indian Journal Of Agricultural Research
Anatomical and physiological traits of broad bean (Vicia faba L.) seedling affected by salicylic acid and salt stress
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A laboratory experiment was carried out at the College of Agriculture University of Baghdad in 2017. The aim was to improve the anatomical and physiological traits of broad bean seedling under salt stress by soaking it in salicylic acid. The concentrations of salicylic acid were 0, 10, and 20 mg L-1 and the electrical conductivity levels were 0, 3, and 6 dS m-1. The complete randomized design was used with four replications. The increasing of salicylic acid concentration up to 10 mg L-1 led to increasing the stem cortex thickness, stem vascular bundles thickness, and root cortex thickness significantly by (34.9,36.7,and 55 μm) respectively, while the treatment of 20 mg L-1 led to decreasing these traits by (28.2, 27.8, and 48.1 μm), compa

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Publication Date
Thu Aug 02 2018
Journal Name
Indian Journal Of Agricultural Research
Anatomical and physiological traits of broad bean (Vicia faba L.) seedling affected by salicylic acid and salt stress
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A laboratory experiment was carried out at the College of Agriculture University of Baghdad in 2017. The aim was to improve the anatomical and physiological traits of broad bean seedling under salt stress by soaking it in salicylic acid. The concentrations of salicylic acid were 0, 10, and 20 mg L-1 and the electrical conductivity levels were 0, 3, and 6 dS m-1. The complete randomized design was used with four replications. The increasing of salicylic acid concentration up to 10 mg L-1 led to increasing the stem cortex thickness, stem vascular bundles thickness, and root cortex thickness significantly by (34.9,36.7,and 55 µm) respectively, while the treatment of 20 mg L-1 led to decreasing these traits by (28.2, 27.8, and 48.1 µm

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