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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
Wed Mar 30 2022
Journal Name
Nasaq Journal
Lingual Sovereignty: Chinua Achebe’s Novel Things Fall Apart A Postcolonial Study
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The discourse surrounding lingual sovereignty within the African postcolonial context is profoundly intertwined with the fabric of cultural identity and self-determination. Language serves not merely as a conduit for communication but as a repository for a people's collective consciousness, encapsulating their traditions, thoughts, and perspectives. In the realm of postcolonial literature, this dialogue often grapples with the paradox of expressing indigenous narratives through the linguistic tools of former colonizers. Chinua Achebe's seminal work, "Things Fall Apart," exemplifies this conundrum, artfully weaving the orature and culture of Umuofia within the English language. Achebe's choice to write in English—a language imposed upon hi

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Publication Date
Sun May 01 2022
Journal Name
Expert Systems With Applications
Novel large scale brain network models for EEG epileptic pattern generations
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Background: Unlike normal EEG patterns, the epileptiform abnormal pattern is characterized by different mor phologies such as the high-frequency oscillations (HFOs) of ripples on spikes, spikes and waves, continuous and sporadic spikes, and ploy2 spikes. Several studies have reported that HFOs can be novel biomarkers in human epilepsy study. S) Method: To regenerate and investigate these patterns, we have proposed three large scale brain network models (BNM by linking the neural mass model (NMM) of Stefanescu-Jirsa 2D (S-J 2D) with our own structural con nectivity derived from the realistic biological data, so called, large-scale connectivity connectome. These models include multiple network connectivity of brain regions at different

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Publication Date
Sat Jan 01 2022
Journal Name
Materials Science For Energy Technologies
New organic PVC photo-stabilizers derived from synthesised novel coumarine moieties
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Publication Date
Tue Sep 03 2019
Journal Name
Rawal Medical Journal
Evaluation of Radial Nerve Injury Associated with Closed Humeral Shaft Fracture by Early Pre-operative Ultrasonic Evaluation and Correlation with Surgical Exploration
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Traumatic radial nerve injury in humeral shaft fracture is the most common traumatic nerve injury in long-bone fracture, with overall prevalence 2-18%, ranging from traction to complete transection. Spontaneous recovery may reach 88%. The aim of the study is to assess the sensitivity & specificity of the ultrasound to detect the radial nerve injury and to see if this can be used as a diagnostic test. This is a prospective study on 17 adult patients with a closed fracture of the humeral shaft, dividing into two groups, the first group of 7 patients had signs and symptoms of radial nerve palsy at presentation and the second group of 10 patients had intact radial nerve function was considered as a control group. All these patients had at leas

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Publication Date
Sat Jun 01 2013
Journal Name
Journal Of Economics And Administrative Sciences
Evaluation of Integrated Information Technology System in Organizations “Exploratory Comparative Search for opinions of sample of Workers in the Faculties of Science & Education AL- Asma'I at the University of Diyala
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       The subject of the information technology system ( ITS ) of the important issues And contemporary thought in management, and various types of organizations seeking to apply and try to

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Publication Date
Sat Jan 01 2022
Journal Name
Revista Electronica De Veterinaria
The Molecular Identification of Pathogenic E. coli Isolated from Raw Cow Milk and Assessment Their Anti-susceptibility to Medical Plants at Al-Najaf city/ Iraq
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Background: Toxin-producing Shiga Escherichia coli has been identified as a new foodborne pathogen that poses a significant health risk to humans. Shiga toxin-producing Escherichia coli can be found in raw cow milk and its derivatives. A small number of Escherichia coli strains that produce shiga toxin are pathogenic. Aim of study: The study aimed to see if there were any virulence genes in 50 milk samples that were typical of Entero-haemorrhagic E. coli and evaluate the Myrtus communis effects on these bacteria. Materials and Method: Milk samples were used to isolate E. coli bacteria (n= 27), biochemically analyzed, and genetically screened for virulence genes using a multiplex (PCR). The hydro-alcoholic extraction of Myrtus communis leave

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Publication Date
Tue Feb 26 2019
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
Role of Managerial Accounting Information System in Improving the Value Chain and its Impaction Evaluation Performance: دراسة حالة في الشركة العامة لصناعة الزيوت النباتية
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The performance measures and traditional methods used in management accounting is no longer able to provide convenient to evaluate the performance of economic units in the modern manufacturing environment information، and so this information is more important and feasibility must be Mistohat of all the company's activities and functions، and it is a problem Find the inadequacy of information management accounting that contribute to meet the needs of the upper levels of management to cope with the problems resulting from the increased size and complexity of the business، and lack of management accounting information and methods used in the performance evaluation، which reflected negatively on the value chain activities and then on the

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Publication Date
Mon Apr 01 2019
Journal Name
Applied Water Science
Hydrochemistry as a tool for interpreting brine origin and chemical equilibrium in oilfields: Zubair reservoir southern Iraq case study
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Publication Date
Wed Jul 01 2015
Journal Name
Al–bahith Al–a'alami
Iraqi Press and its Role in Shaping Electoral Awareness (Iraqi Parliamentary Elections on 30 April, 2014 as a Model)
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The parliamentary election is one of the features of democratic systems that give individuals the right to participate in government and political election-making. Typically, the process of parliamentary elections received wide attention from media, as well as attention from large segments of the public because they understand the vast importance to assume political positions and associated fates of people and their destinies. Its importance comes from the fact that it allows citizens the right to participate in managing the public affairs by granting their confidence and voices to the elected president or his representatives in the parliamentary.
Media task is to emerge democratic societies, in particular, in the mission of urging p

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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)
Nitric Oxide, Peroxynitrite and Malondialdehyde Levels as Markers for Nitrosative/Oxidative Stress in Iraqi Patients with Systemic Lupus Erythematosus
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Systemic lupus Erythematosus is an autoimmune disease of unknown aetiology affecting multiple organ system. Reactive nitrogen and oxygen species are claimed to play a role in this disease. However, the potential of Nitrosative/Oxidative Stress to elicit an autoimmune, response remain till now largely unexplored in humans. This study was done to investigate the status and contribution of nitrosative/oxidative stress in Iraqi patients for systemic lupus erythematosus. Blood samples from 19 patients with systemic lupus erythematosus and 19 age-and sex- matched apparently healthy controls were evaluated for serum levels of nitrosative/oxidative stress markers including nitric oxide, peroxynitrite and malondialdehyde. Nitric oxide levels were

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