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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 29 2023
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
A Review of the Electrical Submersible Pump Development Chronology
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The electric submersible pump, also known as ESP, is a highly effective artificial lift method widely used in the oil industry due to its ability to deliver higher production rates compared to other artificial lift methods. In principle, ESP is a multistage centrifugal pump that converts kinetic energy into dynamic hydraulic pressure necessary to lift fluids at a higher rate with lower bottomhole pressure, especially in oil wells under certain bottomhole condition fluid, and reservoir characteristics. However, several factors and challenges can complicate the completion and optimum development of ESP deployed wells, which need to be addressed to optimize its performance by maximizing efficiency and minimizing costs and uncertainties. To

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Publication Date
Mon Nov 14 2022
Journal Name
Biomedicine
Antibacterial activity of klebocin against methicillin resistance Staphylococcus aureus
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  Introduction and Aim: Bacteriocins are antimicrobial peptides that have bactericidal and/or bacteriostatic activity against other bacteria. The aim of this study was to assess the antibacterial efficiency of Klebocin a K. pneumoniae bacteriocin, against biofilm formation by clinical isolates of methicillin resistant Staphylococcus aureus MRSA.   Materials and Methods: S. aureus isolated from clinical samples was identified according to vitek 2 system Antibiotic susceptibility test was performed according to disc diffusion method. Vitek 2 compact system was also used to detect MRSA strains. Agar well diffusion method was used to evaluate the antibacterial activity of klebocin from K. pneumoniae towards 11 strains of S. aureus by

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Publication Date
Thu Dec 15 2022
Journal Name
Journal Of Baghdad College Of Dentistry
Force degradation of orthodontic elastomeric chains: A literature review
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Background: Elastomeric chains are used to generate force in many orthodontic procedures, but this force decays over time, which could affect tooth movement. This study aimed to study the force degradation of elastomeric chains. Data and Sources: An electronic search on Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, LILACS, and PubMed was made, only articles written in English were included, up to January 2022.Study selection: Fifty original articles, systematic reviews, and RCTs were selected. Conclusion: Tooth movement, salivary enzymes, alcohol-containing mouthwash, whitening mouthwash, and alkaline and strong acidic (pH <5.4) solutions all have a significant impact on elastomeric chain force degradation. The fo

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Publication Date
Tue Jan 06 2026
Journal Name
Frontiers In Mechanical Engineering
Effect of different wing geometries on their vibration characteristics
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Understanding how wing geometry and internal structural configuration influence vibration behavior is essential for ensuring the aeroelastic stability and structural integrity of modern aircraft. This study presents a comprehensive numerical investigation of the modal and deflection characteristics of aircraft wings with different geometries (symmetric tapered planform and swept-back) and spar configurations (box and I-section) using the finite element method (FEM) in ANSYS Mechanical APDL R.15. Six NACA airfoil profiles (0024, 2411, 2416, 2424, 4412, and 4421) with angle of attack 9° under 50 m/s speed and 1,100 kg pay load were analyzed under identical aerodynamic and material conditions using linear elasti

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Publication Date
Thu Nov 02 2023
Journal Name
Journal Of Engineering
Studies on the Moisture Dependent Physical Properties of Cowpea
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Cowpea is a very important legume in Nigeria that is being utilized to Substitute high-cost animal protein for low-income people. The knowledge of some physical properties of various moisture contents is of utmost importance in the design of its handling and processing equipment and machinery, which is the aim of this work, which studied the physical properties of IT99K-573-1-1 (SAMPEA14) variety of Cowpea within 8.77 to 21.58 % db moisture content. The properties studied include Major, Intermediate, and Minor diameters, Sphericity, Surface area, Specific gravity, Volume, Bulk density, 50-tap density, 100-tap density, 1250-tap density, seed mass, Angle of repose, Geometric mean diameter, and Arithmetic mean diameter. The

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Publication Date
Mon Dec 02 2019
Journal Name
Journal Of Mechanics
Fabrics-Shear Strength Links of Silicon-Based Granular Assemblies
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ABSTRACT<p>Silicon (Si)-based materials are sought in different engineering applications including Civil, Mechanical, Chemical, Materials, Energy and Minerals engineering. Silicon and Silicon dioxide are processed extensively in the industries in granular form, for example to develop durable concrete, shock and fracture resistant materials, biological, optical, mechanical and electronic devices which offer significant advantages over existing technologies. Here we focus on the constitutive behaviour of Si-based granular materials under mechanical shearing. In the recent times, it is widely recognised in the literature that the microscopic origin of shear strength in granular assemblies are associated with their</p> ... Show More
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Publication Date
Tue Mar 01 2022
Journal Name
Journal Of Engineering
Removal of Dye from Synthetic Wastewater by Liquid Membrane
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New technologies have risen into popularity causing the Liquid membrane techniques to evolve over other separation techniques due to its high selectivity and recovery, increased fluxes, and reduced investment and operating cost. This work focuses on extracting Methylene Blue (MB), a cationic dye using a simple BLM separation technique from its aqueous phase. It combines extraction and stripping in a single unit operation. The feed phase was an aqueous solution of MB, the solvent chosen was soybean oil for the liquid/organic membrane phase, and tri-octyl amine acted as a carrier. The strip phase was a hydrochloric acid solution for this study. A two-phase equilibrium study was done to choose the correct solvent, carrier,

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Publication Date
Thu Jun 30 2011
Journal Name
Al-khwarizmi Engineering Journal
Evaluating the Performance of Sharq Dijila Water Treatment Plant
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The study aims mainly to evaluate the performance of Sharq Dijila water treatment plant in removing turbidity for the period of 1-4-2001 to 31-3-2004. Daily data for turbidity of raw, clarified, filtered, and supplied water were analyzed. The results of the study showed that there is a wide variation in turbidity levels of raw water fluctuating between 10-1000 NTU with mean value of 41.3 NTU. Turbidity values of the clarified water varied between 1.4-77 NTU. Based on the turbidity value of 10 NTU and 20 NTU (the design maximum turbidity) the readings gave an acceptable percentage of 32.4% and 86% respectively. The turbidity of filtered water ranged between 0.2-4.5 NTU which are completely in compliance with Iraqi and WHO standards. In ac

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Publication Date
Mon Sep 30 2019
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Adsorption of Methyl Orange from Wastewater by using Biochar
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The biochar prepared from sawdust raw material was applied in this study for the treatment of wastewater polluted with methyl orange dye. The effect of pH (2-11), initial concertation (50-250 mg/L) and time were studied. The isotherm of Langmuir, Frendluch and temkin models studied. The Langmuir model was the best to explain the adsorption process, maximum uptake was 136.67 mg/g at 25Co of methyl orange dye. Equilibrium reached after four hours of contact for most adsorbents.The values of thermodynamic parameters ∆G were negative at various temperatures, so the process spontaneous, while ∆H values were 16683 j/mol and ∆S values was 60.82 j/mol.k.

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Publication Date
Fri Sep 24 2021
Journal Name
Proceedings Of Sixth International Congress On Information And Communication Technology
Minimizing Costs of Transportation Problems Using the Genetic Algorithm
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