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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 Jan 01 2020
Journal Name
Journal Of Research In Medical And Dental Science
Evaluation of the Serum Level of Interleukin-6 in Patients Undergoing Surgical Removal of Impacted Mandibular Third Molars
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Evaluation of the Serum Level of Interleukin-6 in Patients Undergoing Surgical Removal of Impacted Mandibular Third Molars, Hussain A Taher*, Salwan Y Bede

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Publication Date
Wed Aug 07 2019
Journal Name
Iraqi National Journal Of Nursing Specialties
Evaluation of Nursing Performance Concerning Nasogastric Tube in Neonatal Intensive Care Unit at al-Batool Teaching Hospital in Baqubah City
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Objectives: The study aim to evaluate nursing performance during nasogastric tube feeding in neonatal intensive care unit. Methodology: A descriptive study was carried out in Neonatal Intensive Care Unit at al–Batool Teaching Hospital, for the purpose of evaluate of quality of nursing performance for premature baby during nasogastric tube feeding in neonatal intensive care unit. The study consumed the period from 4th of December 2017 to the 24nd of April 2018, Non-probability purposive sample of (25) nurses working in the neonatal intensive care unit. The data were collected through the use of Observational instrument which consist of socio-demographic characteristics, quality of nursing care. Results: The study shows that the majority

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Publication Date
Wed Dec 27 2017
Journal Name
Al-khwarizmi Engineering Journal
The Effect of Oil and Filer Contents on the Porosity of Lead Acid Battery Separators Produced From Polyethylene
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                In this investigation a high density polyethylene (HDPE) was used as a substitute to polyvinylchloride in the production of lead acid battery separators. This has been achieved by preparing mixtures of different percentages of the feed materials which include a high density polyethylene (HDPE) locally produced, filler materials such as silica and oils such as dioctylphthalate (DOP) or paraffin which were added to the mixture to improve the final properties of the separator. The materials were compounded by two roll-mills under the same conditions. The following parameters are involved:           &nb

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Publication Date
Sun Jun 06 2010
Journal Name
Baghdad Science Journal
Preparation of Media for Growth and Isolation of Lactic Acid Bacteria by Using the Starch-Industry by- Products
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By- products of corn starch industry were used to prepare media for propagation the lactic acid bacteria as a natural auxotroph. The by- products used were the corn steep water (S) and gluten extract (G) after a proper treatment to get them ready for media preparation. The results showed that it was possible to replace the peptone and meat extract by gluten extract in MRS medium. The growth was approximately similar to that obtained in standard MRS media. Corn steep water (S) was used as well and the growth enhanced by including Tween – 80 at 1% level. The later media named MZ, which was superior for growing standard and local strains and starters. The MZ medium modified by adding acetate and glacial acetic acid similarly to

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Publication Date
Sat Jul 01 2023
Journal Name
Journal Of Materials Science: Materials In Electronics
Effect of phosphoric acid chemical etching on morphological, structural, electrical, and optical properties of porous GaAs Schottky diodes
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Publication Date
Sat Jan 01 2022
Journal Name
Annals Of Parasitology
Evaluation the therapeutic efficacy of different concentration of amphotericin B drug in mice infected with visceral leishmaniosis
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Liposomal amphotericin B (Amph B) has been used effectively to treat leishmaniosis, in spite of its high toxicity appeared in some patients. In our study, Amph B was administered in Leishmania donovani that infected BALB/c male mice using different concentrations to evaluate its efficacy challenge against infection as well as its effect in modulating immunity of the host. We observed that low doses with short duration of Amph B as a therapy regime significantly enhanced the induction of Th1 cytokine (INF-γ), but suppressed Th2 cytokine (IL-10) production. Groups of mice infected with L. donovani and treated with Amph B showed clearly increasing in INF-γ level and reduction in IL-10 level in concentration (3, 4, 5 mg/ml/kg) with best resul

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Scopus
Publication Date
Mon Apr 01 2019
Journal Name
World Heart Journal
Echocardiographic Evaluation of the Right Ventricular Function in a Sample of Iraqi Patients with Left Ventricular Dysfunction
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Background: Assessment of function of the right side of the heart in cases of left ventricular dysfunction has been widely studied but the sensitive and specific echocardiographic parameter to be tested is still a matter of controversy. Right ventricular function is related to left ventricular function by ventricular independence so function of both should be assessed carefully. The objective of this study was to evaluate the effects of left ventricular systolic dysfunction on right ventricular systolic and diastolic functions and pulmonary pressure using conventional and tissue Doppler echocardiography. Patients and Methods: Sixty patients (39 males and 21 females) with heart failure due to left ventricular systolic dysfunction

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Scopus
Publication Date
Sun Apr 30 2023
Journal Name
International Journal Of Design & Nature And Ecodynamics
Evaluation of the Minimum Instream Flow: A Case Study of Shatt-Al Hillah River in Babylon Governorate
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Publication Date
Thu Apr 18 2019
Journal Name
Al-kindy College Medical Journal
Evaluation of Risk Management among Managers of the Primary Health Care Centers in Baghdad City: Comparative Study
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Background: Several risk managem-ent standards had been developed including the Project Management Institute, the National Institute of Standards and Technology, actuarial societies, and ISO standards.

Objective: The study aimed at evaluating risk management among managers of model and ordinary primary health care centers in Baghdad City and comparing the risk management among these centers.

Methods: A descriptive comparative des

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Publication Date
Tue Nov 09 2021
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
The role of international evaluation standards (IVS) in enhancing the quality of financial reporting (appropriate accounting information(
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The research aims to introduce international valuation standards and to identify the relationship between international valuation standards and international accounting and financial reporting standards in enhancing the quality of financial reporting (appropriate accounting information) through the use of statistical models for the purpose of measuring the property of appropriateness of accounting information through the use of statistical models for the purpose of proving the hypothesis that The research referred to it, and accordingly, the Francis and Kothari models were used to measure the appropriateness of accounting information (the quality of the information). The conclusions reached by the two researchers is that the sett

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