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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
Mon Oct 01 2018
Journal Name
Iraqi Journal Of Physics
Spectroscopic analysis of magnesium-aluminum alloys by laser induced breakdown spectroscopy
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In this work, the spectra of plasma glow produced by Nd:YAG laser operated at 1.064 μm on Al-Mg alloys with same molar ratio samples in air were analyzed by comparing the atomic lines of aluminum and magnesium with that of strong standard lines. The effect of laser energies on spectral lines, produced by laser ablation, were investigated using optical spectroscopy, the electron density was measured utilizing the Stark broadening of magnesium-aluminum lines and the electron temperature was calculated from the standard Boltzmann plot method. The results that show the electron temperature increases in magnesium and aluminum targets but decreases in magnesium: aluminum alloy target, also show the electron density increase all the aluminum,

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Publication Date
Sat Dec 01 2018
Journal Name
Al-khwarizmi Engineering Journal
Study the Characterizations of Cement Mortar by Nano Pozzolanic Materials Additions
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This study involves adding nano materials and interaction with cement mortar behavior for several mortar samples under variable curing time with constant water to cement ratio (W/C = 0.5). The effects of adding nano materials on the microstructure of cement mortar were studied by (Scanning Electronic Microscopy (SEM) and X-Ray (for samples at different curing time 28 and 91 days. Small ratio replacements of nano particles (SiO2 or Al2O3) were added to Ordinary Portland Cement (OPC) type (I). The percentage of nano materials additives replacement by weight of ordinary Portland cement includes (1, 2, 3, 4 and 5%) for both types of nano materials with constant (W/C) ratio, also the amount of the fin

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Publication Date
Sat Dec 01 2018
Journal Name
Al-khwarizmi Engineering Journal
Semi-Active Damping of Mechanical Vibrating Systems Using Variable Stiffness Actuator
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      In this research, a variable stiffness actuator is proposed to enhance the damping of the mechanical vibrating system. The frequency response analysis of the vibrating system is dependant in order to analyze and synthesis this semi-active damping, where the suggested process is using active filter to estimate the present frequency of the vibration system, and this will limit the value of the stiffness of the vibrated system. Two active filter s are needed, low-pass-filter (LPF) to choose the higher stiffness of the actuator at small frequencies as well as more damping and high-pass-filter (HPF) to choose the lower stiffness of the actuator at high frequencies as well as more damping, and so

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Publication Date
Fri Jan 01 2016
Journal Name
Journal Of The American Pharmacists Association
Estimating the cost of unclaimed electronic prescriptions at an independent pharmacy
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Publication Date
Sun Sep 07 2008
Journal Name
Baghdad Science Journal
Variables Affecting Developments of Hydroxyapatite Coating by Using Electrophoretic Deposition Technique
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Electrophoretic Deposition (EPD) process offers various advantages like the fabrication of the ceramic coatings and bodies with dense packing, good sinterability and homogenous microstructure. The variables namely (applied potential, deposition time and sintering temperature) affected the development of hydroxyapatite (HAP) coatings. The coating weight and thickness were found to increase with the increase in applied potential or coating time. Sintering temperature was found to affect in change phases of the metal, furthermore the firing shrinkage of the HAP coating on a constraining metal substrate leads to serve cracking. XRD Characterization indicates the formation of a contamination free phase pure, and the optical micrographs show th

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Publication Date
Fri Jan 01 2021
Journal Name
E3s Web Of Conferences
Effect of Halabjah Earthquake on Al-Wand Earth Dam: Numerical Analysis
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The Halabja earthquake occurred on 12/11/2017 in Iraq, with a magnitude of 7.3 Mw, which happened in the Iraqi-Iranian borders. This earthquake killed and injured many people in the Kurdish region in the north of the country. There is no natural disaster more dangerous than earthquake, especially it occurs without warning, great attention must be paid to the impact of earthquakes on the soil and preparing for a wave of earthquakes. Numerical modeling using specific elements is considered a powerful tool to investigate the required behavior of structures in Geotechnical engineering, and the main objective of this is to assess the response of the Al-Wand dam to the Halabja earthquake, as this dam is located in an area that has been su

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Publication Date
Sat Jan 01 2022
Journal Name
Journal Of Ecological Engineering
Biosynthetic of Titanium Dioxide Nanoparticles Using Zizyphus Spina-Christi Leaves Extract
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Publication Date
Wed Jan 25 2023
Journal Name
International Journal Of Biomaterials
Surface Characterization of Stainless Steel 316L Coated with Various Nanoparticle Types
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Background. Material tribology has widely expanded in scope and depth and is extended from the mechanical field to the biomedical field. The present study aimed to characterize the nanocoating of highly pure (99.9%) niobium (Nb), tantalum (Ta), and vanadium (V) deposited on 316L stainless steel (SS) substrates which considered the most widely used alloys in the manufacturing of SS orthodontic components. To date, the coating of SS orthodontic archwires with Nb, Ta, and V using a plasma sputtering method has never been reported. Nanodeposition was performed using a DC plasma sputtering system with three different sputtering times (1, 2, and 3 hours). Results. Structural and elemental analyses were conducted on the deposited coating

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Publication Date
Tue May 23 2023
Journal Name
Journal Of Engineering
REMOVAL OF OIL FROM WASTEWATER BY ADVANCED OXIDATION PROCESS / HOMOGENEOUS PROCESS
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In the present work advanced oxidation process, photo-Fenton (UV/H2O2/Fe+2) system, for the treatment of wastewater contaminated with oil was investigated. The reaction was influenced by the input concentration of hydrogen peroxide H2O2, the initial amount of the iron catalyst Fe+2, pH, temperature and the concentration of oil in the wastewater. The removal efficiency for the system UV/ H2O2/Fe+2 at the optimal conditions and dosage (H2O2 = 400mg/L, Fe+2 = 40mg/L, pH=3, temperature =30o C) for 1000mg/L load was found to be 72%.

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Publication Date
Fri May 03 2024
Journal Name
Journal Of Optics
Transmission Of 10 Gb/s For Underwater Optical Wireless Communication System
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