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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 Apr 01 2020
Journal Name
Indian Journal Of Forensic Medicine & Toxicology
Evaluation of some inflammatory cytokines and glycated hemoglobin in uncontrolled type 2 diabetes mellitus with nephropathy
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Background: Chronic hyperglycemia causes diabetic nephropathy(DN), which is a typical microvascular complication of type 2 diabetes mellitus. The pathogenesis of DN is not fully understanding. The inflammation may possess a significant role in the progression of DN in diabetic patients. Method: The study accomplished at teaching laboratories of medical city, Baghdad, Iraq. It was included 50uncontrolled diabetic type 2 patients with nephropathy, age range (40-78) years and 42 controlled diabetics type 2 without nephropathy, age range (35 - 52) years as a control group. The participants divided in to two groups according to HbA1c measurement which is described as follows: < 7.5% of HbA1c describes controlled diabetes, and > 9% of HbA1c

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Publication Date
Wed Oct 09 2019
Journal Name
Journal Of The College Of Education For Women
Silence as a Means of Communication in Harold Pinter’s The Caretaker
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Harold Pinter’s The Caretaker(1959) clearly portrays a lack of communication among the characters of the play which refers to the condition of modern man. This failure of communication led Harold Pinter to use a lot of pauses and silences in all the plays he wrote instead of words. Samuel Beckett preceded Pinter in doing so in his plays and one way to express the bewilderment of modern man during the 20th century is through the use of no language in the dramatic works. Language is no more important to modern man; instead, he uses silence to express his feelings. Silence is more powerful than the words themselves. That’s why long and short pauses can be seen throughout all Pinter’s plays.

In this play, th

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Publication Date
Tue Jun 01 2021
Journal Name
Iraqi Journal Of Physics
Studying Audio Capacity as Carrier of Secret Images in Steganographic System
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Steganography art is a technique for hiding information where the unsuspicious cover signal carrying the secret information. Good steganography technique must be includes the important criterions robustness, security, imperceptibility and capacity. The improving each one of these criterions is affects on the others, because of these criterions are overlapped each other.  In this work, a good high capacity audio steganography safely method has been proposed based on LSB random replacing of encrypted cover with encrypted message bits at random positions. The research also included a capacity studying for the audio file, speech or music, by safely manner to carrying secret images, so it is difficult for unauthorized persons to suspect

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Publication Date
Wed Mar 02 2022
Journal Name
Journal Of Educational And Psychological Researches
The Role of School Administration in Achieving Educational and Learning Goals as Seen by Educational Supervisors in the Stage of Basic Education
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This study aimed to identify the role of school administration in achieving educational and learning goals from the point of view of educational supervisors in the stage of basic education. The descriptive method was adopted. As for the sample size, it has reached (59) educational supervisors. A questionnaire consisting of 29 paragraphs divided into four areas was used. The data were statistically analyzed on the Chi-square test, the percentage, and the mono-variance analysis. The result showed that the school administration contributes to achieving educational goals. It also works to solve problems in democratic ways, and in modern methods, there are differences in the criteria for choosing the headmaster. The study recommended that sch

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Publication Date
Tue Feb 17 2026
Journal Name
Journal Of Baghdad College Of Dentistry
Validity of computed tomographic in assessment of genial tubercle and anterior mandible as a reference guide to locate osteotomy in genioglossus advancement
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Background: Genioglossus advancement is a surgical procedure to advance the tongue in some patients with obstructive sleep apnea syndrome.The important step in this procedure is that of accurately capturing the bone segment attached to the genioglossus muscle to avoid complications such as mandibular fracture, devitalization of the inferior incisor roots, and incomplete incorporation of the genioglossus Materials and Method: Computed tomography scans were taken for 53 Iraqi adult patients (28 male and 25 female) range from (18-35) years with skeletal class I classification and intact anterior mandible dentition included in this study using sagittal and axial sections. The measurements were done for genial tubercle and anterior mandibular re

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Publication Date
Mon Apr 01 2024
Journal Name
Materials Science In Semiconductor Processing
Rational design of novel 0D/0D Bi2Sn2O7/CeO2 in the core-shell nanostructure for boosting the photocatalytic decomposition of antibiotics in wastewater: S-type-based mechanism
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Publication Date
Sun Jun 30 2024
Journal Name
Lark
The Image of the Arab in Hebrew Literature for Young Adults – A Reading of the Novel “Nadia” by Kalila Ron Feder
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يهدف هذا البحث الى التطرق الى صورة العربي كما يعرضها ادب اليافعين العبري في رواية " نادية " للكاتبة العبرية " كاليلا رون فيدر " . والتي تعد من الاديبات العبريات اللواتي تطرقن بصورة مباشرة الى موضوع ما خلف الجدار ، والصراع العربي – الإسرائيلي وانعكاساته على المجتمع الإسرائيلي بصورة عامة والمجتمع العربي بصورة خاصة . ينقسم هذا البحث إلى ثلاثة فصول، تطرق الفصل الأول  إلى "ادب اليافعين"، و تاريخه ، مميزاته والفئ

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Publication Date
Sat Dec 01 2018
Journal Name
Journal Of Pharmaceutical Sciences And Research
Pryparation, characterization and biological activity of new derivatives of 2-biphenyl-3-aminomethylimidazo(1,2-a)pyrimidine
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New Fourteen compounds were synthesized in four steps. The first step included synthesis of 2-biphenyl fused ring of imidazo(1,2- a)pyrimidine from the reaction of 2-aminopyrimidine and biphenyl phenacyl bromide . The second step was introduced aldehyde group from the reaction of 2-biphenyl fused rings of imidazo(1,2-a)pyrimidine with POCl3 in presence of DMF and CHCl3. 3-Carbaladehyde derivatives of fused imidazo/pyrimidine was reacted with different aromatic amines to afford new Schiff bases. These new 3- imines derivatives was reduced by using sodiumborohydride to yield another new 3-aminomethyl-2-biphenyl imidazo (1,2-a)pyrimidine derivatives in moderate yield .Some new prepared compounds were identified by melting point, FT- IR , 13C-

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Publication Date
Fri Feb 01 2019
Journal Name
Journal Of Economics And Administrative Sciences
Adopting IPSASs and its impact on the quality of financial reporting and performance evaluation in Iraqi government units
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Abstract

     Performance evaluation is of great importance in all countries of the world, because it has a prominent and effective role in determining the efficiency and effectiveness of the optimal use of available resources, which are rare and important in achieving the desired objectives. With the continued growth of public spending and the limited resources, the State seeks to achieve its objectives through its units with minimal expenditure or deficit, rationality and wastefulness in the spending. In many countries, particularly developing countries, reforms are made in the public sector to achieve that goal through the adoption of IPSAS, which is reflected in the developmen

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Publication Date
Sat Jul 30 2016
Journal Name
Hepatology
Farnesoid X receptor activation increases reverse cholesterol transport by modulating bile acid composition and cholesterol absorption in mice
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Activation of farnesoid X receptor (FXR) markedly attenuates development of atherosclerosis in animal models. However, the underlying mechanism is not well elucidated. Here, we show that the FXR agonist, obeticholic acid (OCA), increases fecal cholesterol excretion and macrophage reverse cholesterol transport (RCT) dependent on activation of hepatic FXR. OCA does not increase biliary cholesterol secretion, but inhibits intestinal cholesterol absorption. OCA markedly inhibits hepatic cholesterol 7α‐hydroxylase (Cyp7a1) and sterol 12α‐hydroxylase (Cyp8b1) partly through inducing small heterodimer partner, leading to reduced bile acid pool size and al

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