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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
Thu Jun 27 2024
Journal Name
Iraqi Journal Of Pharmaceutical Sciences
Synthesis, Characterization and Anticancer Activity of Chitosan Schiff Base / PEG Blend Doped with Gold and Silver Nanoparticles in Treatment of Breast Cancer Cell Line MCF-7
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In the present study, chitosan Schiff base has been prepared from chitosan reaction with p-chloro benzaldehyde. The AuNPs and AgNPs were manufactured by extract of onion peels as a reducing agent. The AuNPs and AgNPs that have been synthesized were characterized through UV-vis spectroscopy, XRD analyses and SEM microscopy. The polymer blends of the chitosan / PEG has been prepared by using the approach of solution casting. Chitosan Schiff base / PEG Au and Ag nanocomposites were synthesized, nanocomposites and polymer blends have been characterized by FTIR which confirm the formation of Schiff base by revealing a new band of absorption at 1693 cm-1 as a result of the (C=N) imine group. FESEM, DSC and TGA confirm the thermal stability

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Publication Date
Sat Sep 01 2018
Journal Name
Journal Of Interdisciplinary Nanomedicine
Evaluation of intraductal delivery of poly(ethylene glycol)‐doxorubicin conjugate nanocarriers for the treatment of ductal carcinoma in situ (DCIS)‐like lesions in rats
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Abstract<p>Ductal carcinoma in situ is the most commonly diagnosed early stage breast cancer. The efficacy of intraductally delivered poly(ethylene glycol)‐doxorubicin (PEG‐DOX) nanocarriers, composed of one or more DOX conjugated to various PEG polymers, was investigated in an orthotopic ductal carcinoma in situ‐like rat model. In vitro cytotoxicity was evaluated against 13762 Mat B III cells using MTT assay. The orthotopic model was developed by inoculating cancer cells into mammary ducts of female Fischer 344 retired breeder rats. The ductal retention and in vivo antitumour efficacy of two of the six nanocarriers (5 kDa PEG‐DOX and 40 kDa PEG‐(DOX)<sub>4</sub>) were investigated based o</p> ... Show More
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Publication Date
Mon Jun 01 2009
Journal Name
Journal Of Economics And Administrative Sciences
Evaluation of performance of some industrial companies In the default reference comparison method Field study in the public companies of cement (Iraqi - North - South
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The increasing Global Competitive and the continuous improvement in information technology has led the way to the development of the modern systems and using modern techniques. One of these techniques is benchmarking style and Total Quality Management all of them are used to improve the production process and target rid from the losts on the other side.

The Benchmarking style has become a very important for all the industrial systems and the serving systems as well. And an instrument to improve their performance specially those which are suffering from the highness of the costs or waste in time on the other side.

This study aims to depend on virtual Benchmarking style in the eval

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Publication Date
Sun Oct 21 2018
Journal Name
Al-kindy College Medical Journal
Evaluation of the clinical examination in thediagnosis of acute medial collateral ligament injury of the knee joint in comparism with examination under general anesthesia
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Background: Tear of MCL of the knee is a frequent problem among knee ligaments injuries.Injuries to the MCL are usually caused by contact on the outside of the knee and are accompanied by sharp pain on the inside of the knee. Contrary to most other knee ligaments the medial collateral ligament (MCL) has an excellent ability to heal, being fairly large and well vascularised structure. The vast majority of isolated medial ligament injuries heal without significant long-term problems

Objectives: is to compare between the early clinical examination, and assessment under general anesthesia (GA), and to find out the best methods to assess the MCL tear especially in suspected cases.

Type

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Publication Date
Thu Nov 01 2018
Journal Name
Iraqi National Journal Of Nursing Specialties
Evaluation of the performance of private hospitals from the point of view of the beneficiaries (A field Study in the private Sector hospitals in Baghdad)
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Objectives: This Paper is an attempt to evaluate the services provided by the private hospitals
and to identify the strength and weakness in
their performance The results can be utilized in stating conclusion and recommendations to improve
and activate the role of private medical sector in society .
Methodology: A questionnaire has be designed for this purpose and distributed to ( 132 ) beneficiaries
mostly from Baghdad private hospitals .
Results: The paper has come out with many important results . Among These are the following :
* these who benefit from services provided by private hospitals believe that the good performance of
such hospital is not due to the medical services alone but also to scientific aspect

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Publication Date
Thu Mar 25 2021
Journal Name
International Journal Of Drug Delivery Technology
Synthesis, Structural Study, and Biological Activity Evaluation of VO(II), Mn(II), Co(II), Ni(II), Cu(II), Zn(II), Cd(II), and Hg(II) Complexes with New Schiff Base Ligand Derived from Pyrazine
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New Schiff base [3-(3-acetylthioureido)pyrazine-2-carboxylic acid][L] has been prepared through 2 stages, the chloro acetyl chloride has been reacting with the ammonium thiocyanate in the initial phase for producing precursor [A], after that [A] has been reacting with the 3-amino pyrazine-2-carboxilic acid to provide a novel bidentate ligand [L], such ligand [L] has been reacting with certain metal ions in the Mn(II), VO(II), Ni(II), Co(II), Zn(II), Cu(II), Hg(II), and Cd(II) for providing series of new metal complexes regarding general molecular formula [M(L)2XY], in which; VO(II); X=SO4,Y=0, Co(II), Mn(II), Cu(II), Ni(II), Cd(II), Zn(II), and Hg(II); Y=Cl, X=Cl. Also, all the compounds were characterized through spectroscopic techniques [

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Publication Date
Tue Apr 02 2024
Journal Name
Iraqi Journal Of Applied Physics
Evaluation of Corrosion Resistance of Laser-Treated and PEKK-Coated Titanium
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This research focuses on improvement of the corrosion behaviour of commercial pure titanium (Ti) grade II when exposed to Hank’s solution through different surface treatments. The disc shape of titanium samples were constructed to be divided according to their surface treatment. The first experimental group the Ti sample was exposed to computer numerical control (CNC) fiber laser machine. Whereas, the other experimental group the Ti sample was only coated with Polyetherketon keton (PEKK) by using carbon dioxide (CO2) laser technique while the last experimental group the Ti sample was treated with CNC fiber laser followed by PEKK coating by using CO2 laser technique. All were compared with the untreated control group. The electrochemical a

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Publication Date
Sun Oct 02 2022
Journal Name
Clinical Medicine And Medical Research.
Evaluation of Aesthetic Outcome and Safety of Lipoabdominoplasty for Abdominal Contouring
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Background: Abdominoplasty is one of the commonest surgical procedures that performed for those patients who had skin laxity, strive and muscle rectur diastasis. Combined using of liposuction and abdominoplasty it can give better result than traditional abdominoplasty with fear complications. Patient and Method: A total number of 25 female patients with age ranging between 27-55 years were underwent lipoabdominoplasty. With extensive liposuction of abdominal wall and selective undermining together with muscle plication. All of our patients had body mass index more than 30. Patients satisfaction and complication were documented postoperatively. Result: All of our patients had no Major complications and the postoperative period passed unevent

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Publication Date
Mon Dec 30 2013
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Permeability Prediction of Un-Cored Intervals Using FZI Method and Matrix Density Grouping Method: A Case Study of Abughirab Field/Asmari FM., Iraq
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Knowledge of permeability is critical for developing an effective reservoir description. Permeability data may be calculated from well tests, cores and logs. Normally, using well log data to derive estimates of permeability is the lowest cost method. This paper will focus on the evaluation of formation permeability in un-cored intervals for Abughirab field/Asmari reservoir in Iraq from core and well log data. Hydraulic flow unit (HFU) concept is strongly related to the flow zone indicator (FZI) which is a function of the reservoir quality index (RQI). Both measures are based on porosity and permeability of cores. It is assumed that samples with similar FZI values belong to the same HFU. A generated method is also used to calculate permea

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Publication Date
Fri Dec 01 2023
Journal Name
Baghdad Science Journal
Synthesis of Carbon Nanotubes Using Modified Hummers Method for Cathode Electrodes in Dye-Sensitized Solar Cell
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      In this research, carbon nanotubes (CNTs) is prepared  through the Hummers method with a slight change in some of the work steps, thus, a new method has been created for preparing carbon nanotubes which is similar to the original Hummers method that is used to prepare graphene oxide. Then, the suspension carbon nanotubes is transferred to a simple electrode position platform consisting of two electrodes and the cell body for the coating and reduction of the carbon nanotubes on ITO glass which represents the cathode electrode while platinum represents the anode electrode. The deposited layer of carbon nanotubes is examined through the scanning electron microscope technique (SEM), and the images throughout the research show the

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