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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
Fri Mar 01 2024
Journal Name
Baghdad Science Journal
Preparing a New Type of Concrete Based on Sulfur-melamine Modifier
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In this research work, a new type of concrete based on sulfur-melamine modification was introduced, and its various properties were studied. This new type of concrete was prepared based on the sulfur-melamine modification and various ingredients. The new sulfur-melamine modifier was fabricated, and its fabrication was confirmed by IR spectroscopy and TG analysis. The surface morphology resulted from this modifier was studied by SEM and EDS analysis. The components ratios in concrete, chemical and physical characteristics resulted from sulfur-melamine modifier, chemical and corrosion resistance of concrete, stability of concrete against water adsorption, stability of concrete against freezing, physical and mechanical properties and durabi

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Publication Date
Wed Jan 01 2020
Journal Name
Society Of Petroleum Engineering
Stress-dependent petrophysical properties of high heterogeneous carbonate tight oil reservoirs
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Publication Date
Fri May 01 2020
Journal Name
Iop Conference Series: Materials Science And Engineering
A review of ultra-high temperature materials for thermal protection system
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Abstract<p>Ultra-High Temperature Materials (UHTMs) are at the base of entire aerospace industry; these high stable materials at temperatures exceeding 1600 °C are used to manage the heat shielding to protect vehicles and probes during the hypersonic flight through reentry trajectory against aerodynamic heating and reducing plasma surface interaction. Those materials are also recognized as Thermal Protection System Materials (TPSMs). The structural materials used during the high-temperature oxidizing environment are mainly limited to SiC, oxide ceramics, and composites. In addition to that, silicon-based ceramic has a maximum-use at 1700 °C approximately; as it is an active oxidation process o</p> ... Show More
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Publication Date
Wed Jul 01 2020
Journal Name
Ieee Transactions On Industrial Electronics
Finite-Time Continuous Terminal Sliding Mode Control of Servo Motor Systems
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In this article, a continuous terminal sliding mode control algorithm is proposed for servo motor systems. A novel full-order terminal sliding mode surface is proposed based on the bilimit homogeneous property, such that the sliding motion is finite-time stable independent of the system’s initial condition. A new continuous terminal sliding mode control algorithm is proposed to guarantee that the system states reach the sliding surface in finitetime. Not only the robustness is guaranteed by the proposed controller but also the continuity makes the control algorithm more suitable for the servo mechanical systems. Finally, a numerical example is presented to depict the advantages of the proposed control algorithm. An application in the rota

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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
Thu Jun 16 2022
Journal Name
Al-khwarizmi Engineering Journal
Intelligent Tuning Control of two Link Flexible Manipulator with Piezoelectric Actuator
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This paper represents an experimental study on the application of smart control represented by the use of the fuzzy logic controller. Two-link flexible manipulators that are used in airspace and military applications are made of flexible materials characterized by low frequency and damping ratio. To solve this problem, this paper proposes the use of smart materials (piezoelectric transducers), where each link is bonded with a pair of piezoelectric transducers that act as a sensor and another as an actuator. As the arm vibrates because of the movement generated by the motor, this voltage is controlled by a regulator inside the LABVIEW® 2020 software and sends the output control voltage to the piezoelectric actuator. Experimental results

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Publication Date
Tue Sep 08 2020
Journal Name
Baghdad Science Journal
Matrix Form of Deriving High Order Schemes for the First Derivative
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For many problems in Physics and Computational Fluid Dynamics (CFD), providing an accurate approximation of derivatives is a challenging task. This paper presents a class of high order numerical schemes for approximating the first derivative. These approximations are derived based on solving a special system of equations with some unknown coefficients. The construction method provides numerous types of schemes with different orders of accuracy. The accuracy of each scheme is analyzed by using Fourier analysis, which illustrates the dispersion and dissipation of the scheme. The polynomial technique is used to verify the order of accuracy of the proposed schemes by obtaining the error terms. Dispersion and dissipation errors are calculated

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Publication Date
Wed Dec 30 2020
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Elimination of Congo Red Dyes From Aqueous Solution Using Eichhornia Crassipes
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   Water hyacinth (Eichhornia crassipes) is a free-floating plant, growing plentifully in the tropical water bodies. It is being speculated that the large biomass can be used in wastewater treatment, heavy steel and dye remediation, as a substrate for bioethanol and biogas production, electrical energy generation, industrial uses, human food and antioxidants, medicines, feed, agriculture, and sustainable improvement. In this work, the adsorption of Congo Red (CR) from aqueous solution onto EC biomass was investigated through a series of batch experiments. The effects of operating parameters such as pH (3-9), dosage (0.1-0.9 g. /100 ml), agitated velocity (100-300), size particle (88-353μm), temperature (10-50˚C), initial dye

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Publication Date
Thu Aug 01 2019
Journal Name
Iop Conference Series: Materials Science And Engineering
Effect of Embedment Depth on Raft Foundation Settlement Under Seismic Load
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Abstract<p>Dynamic loads highly influence soil properties and may cause real damage to structures and buildings. This article reports the experimental results from 24 tests to study the settlement of flexible and rigid raft foundation with different embedment depth rested on dense sandy soil. A small scale building model of dimension 200*200 mm and 320 mm in height was performed with reinforced concrete raft foundation of 10 mm thickness for flexible raft and 23 mm for rigid raft, The shaking table technique was used to simulate the seismic effect, the shaker was sat to give three different excitation frequencies 1,2,and3 Hz and displacement amplitude equal to 13 mm, the foundation was placed at</p> ... Show More
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