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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
Wed Dec 12 2018
Journal Name
Iop Conference Series: Materials Science And Engineering
Extraction of Essential Oil from Iraqi<i>Eucalyptus Camadulensis</i>Leaves by Water Distillation Methods
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The extraction of Eucalyptus oil from Iraqi Eucalyptus Camadulensis leaves was studded using water distillation methods. The amount of Eucalyptus oil has been determined in a variety of extraction temperature and agitation speed. The effect of water to Eucalyptus leaves (solvent to solid) ratio and particle size of Eucalyptus leaves has been studied in order to evaluate the amount of Eucalyptus oil. The optimum experimental condition for the Eucalyptus oil extraction was established as follows: 100˚C extraction temperature, 200 rpm agitation speed; 0.5 cm leave particle size and 6:1 ml: g amount of water to eucalyptus leaves Ratio.

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Publication Date
Fri May 01 2015
Journal Name
Transplantation Proceedings
Prevalence of Polyomavirus Among United Arab Emirates Kidney Transplant Recipients: Results From a Single Center
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Publication Date
Mon Jun 30 2025
Journal Name
Scripta Medica
Case Report: A Rare Presentation of Sigmoid Volvulus During Pregnancy With an Integrative Postoperative Approach
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Publication Date
Tue Oct 07 2003
Journal Name
University Of Baghdad
A STUDY ON SOLVENT EXTRACTION OF HOLMIUM (III) WITH SUDAN BLACK B REAGENT (M.Sc. Thesis)
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Publication Date
Sun Jun 07 2015
Journal Name
Baghdad Science Journal
A Solution of Second Kind Volterra Integral Equations Using Third Order Non-Polynomial Spline Function
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In this paper, third order non-polynomial spline function is used to solve 2nd kind Volterra integral equations. Numerical examples are presented to illustrate the applications of this method, and to compare the computed results with other known methods.

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Publication Date
Wed Dec 25 2019
Journal Name
Journal Of Engineering
Corrosion Rate Optimization of Mild-Steel under Different Cooling Tower Working Parameters Using Taguchi Design
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This study investigates the implementation of Taguchi design in the estimation of minimum corrosion rate of mild-steel in cooling tower that uses saline solution of different concentration. The experiments were set on the basis of Taguchi’s L16 orthogonal array. The runs were carried out under different condition such as inlet concentration of saline solution, temperature, and flowrate. The Signal-to- Noise ratio and ANOVA analysis were used to define the impact of cooling tower working conditions on the corrosion rate. A regression had been modelled and optimized to identify the optimum level for the working parameters that had been founded to be 13%NaCl, 35ᴼC, and 1 l/min. Also a confirmation run to establish the p

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Publication Date
Sat Sep 30 2023
Journal Name
Misan Journal For Academic Studies
The microhardness Property of the Biomedical commercially pure titaniumstrontium oxide composite alloy after anodic oxidation
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Publication Date
Sun Dec 04 2022
Journal Name
Jordan Journal Of Biological Sciences
The Biological Effect of ZnO Nanoparticles Produced by Using Petroselinum crispum Extract against Candida spp
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Non-thermal or cold plasma create many reactive species and charged particles when brought into contact with plant extracts. The major constituents involve reactive oxygen species, reactive nitrogen species and plasma ultra-violets. These species can be used to synthesize biologically important nanoparticles. The current study addressed the effect of the green method-based preparation approach on the volumetric analysis of Zn nanoparticles. Under different operating conditions, the traditional thermal method and the microwave method as well as the plasma generation in dielectric barrier discharge reactor were adopted as a preparation approach in this study. The results generally show that the type of method used plays an important rol

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Publication Date
Sat Jan 01 2011
Journal Name
Iraqi Journal Of Physics
Calculation of Particle Emission Rates for Nucleon-Induced Reactions with non-Equidistance Spacing Model Dependence
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Nuclear emission rates for nucleon-induced reactions are theoretically calculated based on the one-component exciton model that uses state density with non-Equidistance Spacing Model (non-ESM). Fair comparison is made from different state density values that assumed various degrees of approximation formulae, beside the zeroth-order formula corresponding to the ESM. Calculations were made for 96Mo nucleus subjected to (N,N) reaction at Emax=50 MeV. The results showed that the non-ESM treatment for the state density will significantly improve the emission rates calculated for various exciton configurations. Three terms might suffice a proper calculation, but the results kept changing even for ten terms. However, five terms is found to give

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Publication Date
Fri Jan 01 2016
Journal Name
Journal Of Engineering
Improve the Performance of PID Controller by Two Algorithms for Controlling the DC Servo Motor
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The paper uses the Direct Synthesis (DS) method for tuning the Proportional Integral Derivative (PID) controller for controlling the DC servo motor. Two algorithms are presented for enhancing the performance of the suggested PID controller. These algorithms are Back-Propagation Neural Network and Particle Swarm Optimization (PSO). The performance and characteristics of DC servo motor are explained. The simulation results that obtained by using Matlab program show that the steady state error is eliminated with shorter adjusted time when using these algorithms with PID controller. A comparative between the two algorithms are described in this paper to show their effectiveness, which is found that the PSO algorithm gives be

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