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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 Mar 01 2021
Journal Name
Journal Of Dental Sciences
Evaluation of the efficacy of lycopene gel compared with minocycline hydrochloride microspheres as an adjunct to nonsurgical periodontal treatment: A randomised clinical trial
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Publication Date
Wed Mar 30 2022
Journal Name
Journal Of Educational And Psychological Researches
Anger in Kindergarten Children as Seen by Teachers
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Anger is one of the problems of scientific importance that psychologists and education scientists are interested in, especially societies and educational environments, because if a child’s anger continues to develop into violence, then it becomes an unusual behavior, and an indication of the child's lack of adaptation to his family and his environment (Moses, 2013: 4)                                                               &n

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Publication Date
Sun Feb 10 2019
Journal Name
Journal Of The College Of Education For Women
Arthur Miller’s Tragedy as Reflected in The Crucible
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In the period immediately following the end of World War II, American theatre was transformed by the work of playwright Arthur Miller. Miller tapped into a sense of dissatisfaction and unrest within the greater American psyche because he was profoundly influenced by the depression and the war that immediately followed it. His dramas proved to be both the conscience and redemption of the times; allowing people an honest view of the direction the country had taken.1 Miller has his own concept of tragedy as a modern playwright. He believes that tragedy may depict ordinary people in domestic surroundings instead of talking about a character from a high rank, a king or a queen. Miller’s main concern lies in dramatizing the whole man as he i

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Publication Date
Sun Dec 01 2024
Journal Name
مجلة كلية التربية للبنات/ الجامعة العراقية
HURIER Model as a Model in Language Teaching
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Between the 1980s and 1990s, the HURIER model was developed by Brownell and consist of six interrelated components, which are represented in these acronyms (Hearing, Understanding, Remembering, Interpreting, Evaluating, and Responding). This model can be considered as a framework of the behavioral approach which can be used to improve students’ listening performance and to foster a positive attitude toward listening. Many learners find it challenging to improve their listening skills when learning a second or foreign language because it requires the integration of both listening and speaking. Consequently, enhancing this skill will help students improve other language skills, including reading, speaking, and writing. The HURI

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Publication Date
Fri Jan 01 2016
Journal Name
Al-ustath Journal For Human And Social Sciences
Infinitive Clauses as Matrix Verbs Complementationi in Shakespeare
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The aim of this research is to find out why some matrix verbs are no longer complemented by the two types of infinitive clauses as it is the case in Elizabethan English . At that time (when Shakespeare was writing ), the same matrix verb triggers the two types of infinitive clauses as its complex transitive complementation .Such free variation is not possible in Present –Day English . In this corpus – based study , it is shown that the choice of the form of the infinitive clause is not free; there are certain syntactic ,sem- antic constraints that dete, - infinitive.

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Publication Date
Sun Sep 07 2014
Journal Name
Baghdad Science Journal
Heat Shock Protein70 as Biomarker in Bladder Cancer
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The present study aimed to shed light on the urine HSP70 concentration of patients with urinary bladder carcinoma UBC and control subjects as new urinary biomarker. The second aim was to associate this protein concentration with UBC stage and grade in patients with UBC. A direct ELISA was used to quantify urine HSP concentrations in 58 patients with urinary bladder carcinoma UBC with different grades (G) and stages (T) all malignant of them was transitional cell carcinoma (TCC) type , 15 from patients with urinary Bladder disorders other than cancer UBD and 15 healthy subjects(control) . Urine concentrations of HSP70 were elevated in patients with UBC compared to those without UBC (healthy and UBD, P< 0.5). There was a high signifi

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Publication Date
Fri May 21 2021
Journal Name
International Journal Of Pavement Research And Technology
Developing Resilient Modulus Prediction Models Based on Experimental Results of Crushed Hornfels Mixes with Different Gradations and Plasticity
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Publication Date
Sun Jan 01 2023
Journal Name
Journal Of Pakistan Association Of Dermatologists
The role of epigenetics in immunosuppression in patients with infectious diseases as a fascinating applied observation
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Publication Date
Sat Oct 01 2022
Journal Name
Baghdad Science Journal
Assessment of Obesity, Dyslipidemia, Hyperglycemia, and Pro-Inflammatory Cytokines as Cardiovascular Disease Risk Factors in Acromegaly Patients
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Cardiovascular disease is one of the most common comorbidities associated with enlarged extremities, occurring in 60 % of patients with acromegaly. The aim of this study is to evaluate the relationship of growth hormone and insulin such as growth factor-1 with obesity, dyslipidemia, hyperglycemia, and pro-inflammatory cytokines (IL-2, IL-6, IL-10), as risk factors for cardiovascular disorder in acromegaly patients. Eighty subjects were included and categorized into two groups: 40 acromegaly patients and 40 of the control group. The results indicated weight excess, hyperglycemia, hypertension, lipid disorder, and elevated levels of interleukins (2, 6, and 10). The correlation of both GH and IGF-1 with each of weight, BMI, systolic blood p

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Publication Date
Fri Mar 01 2024
Journal Name
الذكوات البيض
The problem of employing political discourse and its role in promoting community peace: Iraq as a model
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After 2003, Iraq witnessed new challenges represented by the predominance of sectarian discourses, hatred and extremism at the expense of moderate political discourse and the predominance of sub-affiliations and external agendas at the expense of national affiliation, which led to the creation of an unsafe or stable environment dominated by the character of violence and terrorism. Moderate discourse would work to fuse sub-affiliations into one melting pot in which it would be the first loyalty to the homeland and not to the tribe, party or sect... Etc., and this in turn will contribute to promoting peaceful coexistence between the various other sub-affiliations within the framework of one community construction