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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
Sat Oct 01 2011
Journal Name
Iraqi Journal Of Physics
The Effect of metals as additives on adhesion properties of epoxy resin
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EP/ metal composites were prepared as adhesives between two steel rods. Epoxy resin (EP) was used as a matrix with metal as fillers (Al, Cu, Fe,).
The preparation method for tensile adhesion tests includes two steel rods with adhesive composites between the rods to measure adhesion strength Sad and adhesion toughness Gad.
Results of tensile adhesion tests show that EP/ metals composite have maximum strength Sad for certain weight percentage of metals 2.95 and 9MPa at 10% for EP/Al and EP/Cu composite and 8.2MPa at 40% for EP/Fe composites

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Publication Date
Mon Nov 01 2010
Journal Name
Iraqi Journal Of Physics
The Effect of metals as Additives on Thermal conductivity of Epoxy Resin
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A hand lay-up method was used to prepare Epoxy/ metal composites. Epoxy resin (EP) was used as a matrix with metal particles (Al, Cu, and Fe) as fillers.
The preparation method includes preparing square panels of composites with different weight percentage of fillers (10, 20, 30, 40, and 50%). Standard specimens (88mm in diameter) for thermal conductivity tests were prepared to measure thermal conductivity kexp.The result of experimental thermal conductivity kexp, for EP/metal composites show that, kexp increase with increasing weight percentage, For EP/ Al and EP/Cu composites, and it have have maximum values of 0.33 and 0.35 W/m.K, respectively. While kexp for EP/ Fe composite show slight increase with maximum value of 0.186 W/m.K.

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Publication Date
Mon Mar 08 2021
Journal Name
Baghdad Science Journal
Determination of the neutron refleetion coefficient as a function of reflector material
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This work presents a simple method for determination of the neutron reflection coefficient (n) as a function of different neutron reflector materials.A laboratory neutron source (Am-Be) with activity of 16 ci is employed with a (BF3) neutron detector. Am-BeThree types of reflector materials are used as samples, the thickness of each sample is (5cm).It is found that( ?7) is: -For polyethlyene = 0.818

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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)
Preparation of a New Dosage Form of Metoclopramide Hydrochloride as Orodispersible Tablet
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Metoclopramide HCl (MTB) is a potent antiemetic drug used for the treatment of nausea and vomiting. Many trials were made to prepare a satisfactory MTB orodispersible tablet using direct compression method.Various super disintegrants were used in this study which are croscarmellose sodium (CCS), sodium starch glycolate (SSG) and crospovidone (CP). The latter was the best in terms of showing the fastest disintegration time in the mouth.Among the different diluents utilized, it was found that a combination of microcrystalline cellulose PH101 (MCC 101), mannitol, dicalcium phosphate dihydrate (DPD) and Glycine was the best in preparing MTB orodispersible tablet with fastest disintegration time in the mouth.The physical parameters of the pre

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Publication Date
Mon Sep 30 2002
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
The Treatment of Wastewater of Alcohol Factory by Filtration as Primary Treatment
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Publication Date
Thu Aug 31 2017
Journal Name
Journal Of Engineering
Urban agriculture as one of the ecological applications of the regenerative city
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Recently, several concepts and expressions have emerged that have often preoccupied the world . around the concept of environment and sustainability. This is due to the negative and irresponsible impact of man and his innovations in various industrial and technological fieldsthat have damaged the natural environment. Architecture and cities at the broader level are some of the man made components that caused these negative impacts and in the same time affected by them. What distinguishes architectural and urban projects is the consumption of large . quantities of natural resources and production larger amounts of waste and pollution, along the life of these projects. At the end of the twentieth century and the beginning of the twenty-fir

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Publication Date
Tue Jun 23 2020
Journal Name
Annal S Of Tropical Medicine & Public Health
Histological Evaluation of local application of Phyllunthus amarus extracted powder and its combination with fibronectin protein on Wound Healing of rats
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Background: A wound is defined as a break or damage in the skin, resulting from physical or thermal damage or as a result of the presence of an underlying medical or physical condition. Herbal medicine can be called one of the branches of medicine in various forms.Phyllunthus amarus is a small herb well known for its medicinal properties and widely used worldwide. P. amarus is an important plant of Indian Ayurvedic system of medicine. Fibronectin is a major component of the extracellular matrix. It is secreted by various cells, primarily fibroblasts, as a soluble protein dimer and is then assembled into an insoluble matrix in a complex cell-mediated process. Materials and methods: Forty rats will be subjected for a surgical operation

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Publication Date
Tue Dec 01 2009
Journal Name
Journal Of Economics And Administrative Sciences
Evaluation of the efficiency and effectiveness of the accounting system of the Department of Missions and Cultural Relations (*) at the Office of the Ministry of Higher Education and Scientific Research
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The evaluation and efficiency and effectiveness of account system for the department of delegation and cultural Relationships in the center of ministry of higher Education and Scientific research Considered as a very important and active subjects in the modification of accounting system in this department and to develop it and make it able to make available important and accurate information for the planning requirements and monetary and evaluation performance and to make decisions, besides to develop the performance of Iraqi Cultural departments working abroad and to render its role effective to serve the students of higher education in the progressive Countries to facility its growing in scientific and professional and technica

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Publication Date
Sat Apr 01 2023
Journal Name
Siriraj Medical Journal
The Potential of Vitamin-D-Binding Protein as a Urinary Biomarker to Distinguish Steroid-Resistant from Steroid-Sensitive Idiopathic Nephrotic Syndrome in Iraqi Children
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Objective: To determine the ability of uVDBP to discern SRNS from steroid-sensitive nephrotic syndrome (SSNS) in Iraqi children. Materials and Methods: This cross-sectional study enrolled children with SRNS (n=31) and SSNS (n=32) from the pediatric nephrology clinic of Babylon Hospital for Maternity and Pediatrics over three months. Patients' characteristics in terms of demographics, clinical data, and urinary investigations were collected. Quantitative analysis of uVDBP levels was undertaken via a commercially available ELISA kit. Results: The median uVDBP values were significantly higher (p-value<0.001) in the SRNS group (median=10.26, IQR=5.91 μg/mL) than in the SSNS group (median=0.953, IQR=4.12 μg/mL). A negative correlati

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Publication Date
Fri Dec 01 2017
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
Determining the Optimal Ratio of Liquidity in Iraqi Commercial Banks for period (2005-2013): applied research using Iraqi Commercial Banks as a sample study
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  This study  focused on a fundamental issue which was represented by ability of Iraqi central bank in facing the difficulty of determining  the optimal ratio of liquidity in the Iraqi banks in terms of the balancing between its obligations to the depositors and borrowers, and liquidate their funds on one hand and the risks on the other hand.the search aimed  for achieving the goals which represented by identifying the possibility of Iraqi banks to apply the regulations rules and  instructions  issued by central bank  of  Iraq in determining  ratio  of  liquidity and  its  appropriate with Iraqi  banks  action to implement  a  reasonable  profit to&

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