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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 Aug 28 2019
Journal Name
Journal Of Engineering
Evaluation of Heavy Metals Content in Simulated Solid Waste Food Compost
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Composting is one of the solid waste management (SWM) methods where the organic component decomposed biologically under controlled conditions. In this study, a 0.166 m3 bioreactor tank was designed to compose 59.2Kg of simulated common municipal solid food waste having a bulk density, organic matter, organic carbon, pH, nitrogen content, C/N and nitrification index (NH4-N/ NO3-N) of 536.62 kg/m3, 62.34%, 34.76%, 6.53, 1.86%, 23 and 0.34 respectively. The bioreactor operated aerobically for 30 days, and anaerobically for 70 days, until the end of the composting process. Results proved that the composting process could reduce the mass of the waste by 69%.  Nitrogen content,

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Publication Date
Sun Dec 25 2022
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Evaluation of Hepatic Enzymes in major β-thalassemic Patients using Deferasirox
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Abstract

β-thalassemia major is a genetic disease that causes sever defect in normal hemoglobin synthesis. The patients with β-thalassemia major need periodic blood transfusions that can result in accumulation of body iron, so treatment with iron chelating agent is required. Complications of this iron overload affecting many vital organs, including the liver. The aim of this work was to evaluate liver enzymes in β -thalassemia major patients with deferasirox versus without it. Two groups of β-thalassemia major patients were involved in this study named group A; 40 β-thalassemia patients of blood transfusion dependent without deferasirox, group B; 40 β-thalassemia patients of blood transfusion dependent on de

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Publication Date
Tue Jan 02 2024
Journal Name
Turkish Archives Of Pediatrics
Evaluation of Decayed, Missing Due to Caries, and Filled Teeth Index in Children with Phenylketonuria in Comparison to Normal Population
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Publication Date
Thu Nov 08 2018
Journal Name
Iraqi National Journal Of Nursing Specialties
Evaluation of National Standards for Exposure to Chemical Materials and Dusts in the State Company for Drugs Industry in Samarra
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Objective: Evaluation the national standards for exposure to chemical materials and dusts in The State
Company for Drugs Industry in Samarra.
Methodology: A descriptive evaluation design is employed through the present study from 25th May 2011
to 30th November 2011 in order to evaluate the national standards for exposure chemical materials and dusts
in The State Company for Drugs Industry in Samarra. A purposive (non-probability) sample is selected for the
study which includes (110) workers from the State Company for Drugs Industry in Samarra. Data were
gathered through the workers` interviewed according to the nature of work that they perform. The evaluation
questionnaire comprised of three parts which include the w

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Publication Date
Tue Apr 18 2023
Journal Name
Corporate Reputation Review
The Absorptive Capacity of Knowledge as an Approach for Building Strategic Reliability in the Sponge Organizations/Small Organizations in Kirkuk Governorate as a Model
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Publication Date
Thu Mar 30 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
In Vitro Cytotoxic Study for Purified Resveratrol Extracted from Grape Skin Fruit Vitis vinifera
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This study  was  conducted  with the  aim to  extract and  purify  a  polyphenolic  compound  â€œ Resveratrol” from the skin of black grapes Vitis vinifera cultivated in Iraq. The purified resveratrol is obtained after ethanolic extraction with 80% v/v solution for fresh grape skin, followed by acid hydrolysis   with   10%   HCl   solution then   the  aglycon   moiety   was  taken  with   organic   solvent

( chloroform). Using silica gel G60 packed glass column chromatography with mobile phase benzene: methanol: acetic acid  20:4:1 a

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Publication Date
Sun Oct 19 2025
Journal Name
Lecture Notes In Networks And Systems
Analyzing the Pragmatics of Argumentation in the Arabic Novel Using Artificial Intelligence: An Applied Study on the Granada Trilogy
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Publication Date
Sun Sep 07 2014
Journal Name
Baghdad Science Journal
Optimum conditions for ascorbic acid determination in three Iraqi citrus using HPLC technique
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A high-performance liquid chromatography method was employed for the quantitative determination of ascorbic acid (AA) which called vitamin C in three types of Iraqi citrus (orange mandarin and aurantium ) and to establish this goal , evaluation of ascorbic acid degradation is so important due to its significant criticality when exposure to ordinary atmospheric conditions. The chromatographic analysis of AA was carried out after their sequential elution with KH2PO4 ( as mobile phase) by reverse-phase HPLC technique with C8 column and UV detection at 214 nm. .Bad resolutions was appeared clearly for C8 column , so another alternative condition were carried out to improve the resolution by replacement of C8 by C18 column .Statistical treat

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Publication Date
Fri Oct 20 2023
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
Novel Approximate Solutions for Nonlinear Initial and Boundary Value Problems
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This paper investigates an effective computational method (ECM) based on the standard polynomials used to solve some nonlinear initial and boundary value problems appeared in engineering and applied sciences. Moreover, the effective computational methods in this paper were improved by suitable orthogonal base functions, especially the Chebyshev, Bernoulli, and Laguerre polynomials, to obtain novel approximate solutions for some nonlinear problems. These base functions enable the nonlinear problem to be effectively converted into a nonlinear algebraic system of equations, which are then solved using Mathematica®12. The improved effective computational methods (I-ECMs) have been implemented to solve three applications involving nonli

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Publication Date
Sat Mar 01 2025
Journal Name
Iranian Journal Of Immunology
Soluble HLA-E and Gastroesophageal Reflux Disease: A Novel Association
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Gastroesophageal reflux disease (GERD) is a prevalent clinical condition, that affects millions of individuals worldwide. Objective: To assess the level of soluble HLA-E (sHLA-E) as a biomarker in the diagnosis and immunopathogenesis of GERD patients. Methods: The case-control prospective study included 40 GERD patients who were consulted at the Gastroenterology Unit of AlKindy Teaching Hospital, as along with 40 healthy control subjects. The study period extended from January 2023 to May 2024. Blood was drawn from both groups and serum was separated to assesssHLA-E using a sandwich enzyme-linked immunosorbent assay (ELISA) kit. Results: There was a statistically significant difference in sHLA-E levels between GERD patients and healthy cont

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