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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
Tue Aug 30 2022
Journal Name
International Journal Of Research In Social Sciences & Humanities. E-issn
Black poetess, White poems: Phillis Wheatley A Case Study of Hybridity
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Publication Date
Fri Dec 01 2017
Journal Name
Journal Of Economics And Administrative Sciences
Measuring the Stability of Iraqi Banking System according to Basel III
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Banking reforms in many countries have focused on the efficiency enhance of the banking sector, including Iraq, in terms of indicative steps based on recommendations, policies and standards developed by international organizations, foremost of which are Basel III. In this paper, it has tried to highlight the reforms in Basel III and the impact of these reforms on the stability of the banking system in Iraq. As the research derives its importance from the idea that the sound banking system consists of a group of banks capable of employing their assets and obligations efficiently in financial intermediation and enjoying financial solvency. The stability of the banking system is an important factor in achieving the leading role of t

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Publication Date
Thu Feb 01 2024
Journal Name
Baghdad Science Journal
Comparative Study of Gamma- Ray Shielding Parameters for Different Epoxy Composites
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In the current work various types of epoxy composites were added to concrete to enhance its effectiveness as a gamma- ray shield. Four epoxy samples of (E/clay/B4C) S1, (E/Mag/B4C) S2, (EPIL) S3 and (Ep) S4 were used in a comparative study of gamma radiation attenuation properties of these shields that calculating using Mont Carlo code (MCNP-5). Adopting Win X-com software and Artificial Neural Network (ANN), µ/ρ revealed great compliance with MCNP-5. By applying (µ/ρ) output for gamma at different energies, HVL, TVL and MFP have been also estimated. ANN technique was simulated to estimate (µ/ρ) and dose rates. According to the results, µ/ρ of all epoxy samples scored higher than standard concrete. Both S2 and S3 samples having h

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Publication Date
Wed Dec 30 2015
Journal Name
College Of Islamic Sciences
Approvals of the Imam nuclear for Iraqis Through the student platform
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The research was titled: Approval of the Imam of the Nuclear of Iraqis through the curriculum of the students.
The research revolves around the study of the weight of the imam nuclear jurisprudence in which the views of the Iraqi jurists of the Imam Shafi'i agreed through the book of students' approach to the nuclear imam, the research included a brief translation of the nuclear imam, and the definition of his place in the Shafi'i school, and then the definition of Iraqi jurists and then study the jurisprudence The course of research is only three issues, and compared with the views of imams, and the statement of the most correct opinion, and God and the conciliator.
researcher

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Publication Date
Wed Dec 30 2015
Journal Name
College Of Islamic Sciences
The position of the Egyptian public opinion on the Mibi revolution
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The study of the subject of (Egyptian public opinion on the Libyan revolution) came to reveal the role of Egyptian public opinion in mobilizing and solidarity for the masses. With the events witnessed by the Arab countries before the revolution, this was evident by the people 's attitudes towards the tripartite aggression against Egypt in 1956, and the June 1967 war, and the most recent what the Egyptian people showed towards the Libyan revolution. The Egyptian press followed the completion of the arms deal with France and revealed the ability of the Libyan negotiator to achieve moral gain, supported by Egyptian support to thwart the United States intentions to arm "Israel" similarly. The Egyptian people expressed a love for peace and su

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Publication Date
Sun Feb 24 2019
Journal Name
Iraqi Journal Of Physics
Modelling of electron trajectories inside SEM chamber concerning mirror effect phenomenon
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A computational investigation is carried out to describe the behaviour of reflected electrons upon a charged insulator sample and producing mirror effect images. A theoretical expression for the scanning electron path equation is derived concerning Rutherford scattering and some electrostatic aspects. The importance of the derived formula come from its correlation among some of the most important parameters that controls the mirror effect phenomena. These parameters, in fact, are the trapped charges, incident angle and the scanning potential which investigated by considering its influences on the incident electrons. A pervious experimental operation requirements are adopted for operating the introduced expression. However, the obtained r

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Publication Date
Wed Oct 31 2018
Journal Name
Al-kindy College Medical Journal
Leigh Syndrome: Report of a Rare Case with Late Onset Presentation
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Leigh's syndrome, or sub acute necrotizing encephalomyelopathy, is a rare inherited neurometabolic disease of infancy and early childhood with variable course and prognosis. Rarely, it occurs in juveniles and adults. The diagnosis is difficult and still remains to challenge the clinicians on the basis of history; hence the role of imaging is very essential. It is the neuroimaging, chiefly the Magnetic Resonance Imaging showing characteristic symmetrical necrotic lesions in the basal ganglia and/or brain stem that leads to the diagnosis. Late-onset varieties are rare and only few cases were reported all over the world. Here, I report a case of late onset (juvenile) Leigh syndrome presenting with an acute polyneuropathy. Neuroimaging confi

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Publication Date
Mon Sep 30 2002
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Removal of Wool Dyes from Industrial Wastewater by Reverse Osmosis Process
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Publication Date
Sun Mar 01 2015
Journal Name
Journal Of Engineering
Retrofitting of Reinforced Concrete Damaged Short Column Exposed to High Temperature
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Experimental research was carried out to investigate the performance of CFRP wrapping jackets used for retrofitting twelve square reinforced concrete (CR) column specimens damaged by exposure to fire flame, at different temperatures of  300, 500 and 700ºC, except for two specimens that were not burned. The specimens were then loaded axially till failure after gradual or sudden cooling. The specimens were divided into two groups containing two main reinforcement ratios, ρ= 0.0314 and ρ= 0.0542. This was followed by the retrofitting procedure that included wrapping all the specimens with two layers of CFRP fabric sheets. The test results of the retrofitted specimens showed that the fire damaged RC

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Publication Date
Fri Jan 10 2020
Journal Name
Fibers
CFRP Laminates Reinforcing Performance of Short-Span Wedge-Blocks Segmental Beams
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Two of the main advantages of segmental construction are economics, as well as the rapid construction technique. One of the forms of segmental construction, for structural elements, is the segmental beams that built-in short sections, which referred to segments. This research aims to exhibit a new technique for the fabrication of short-span segmental beams from wedge-shaped concrete segments and carbon fiber reinforced polymers (CFRP) in laminate form. The experimental campaign included eight short-span segmental beams. In this study, two selected parameters were considered. These parameters are; the number of layers of CFRP laminates and the adhesive material that used to bond segments to each other, forming short-span segmental be

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