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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 Jul 01 2021
Journal Name
Journal Of Applied Sciences And Nanotechnology
Homogeneity of Lithium Metasilicate-Copper Oxide Glass-Ceramics by Weibull Modulus
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Publication Date
Sat May 01 2021
Journal Name
Journal Of Physics: Conference Series
The Bifurcation Analysis of Food Web Prey- Predator Model with Toxin
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Abstract<p>Local and global bifurcations of food web model consists of immature and mature preys, first predator, and second predator with the current of toxicity and harvesting was studied. It is shown that a trans-critical bifurcation occurs at the equilibrium point <italic>E</italic> <sub>0</sub>, and it revealed the existence of saddle-node bifurcation occurred at equilibrium points <italic>E</italic> <sub>1</sub>, <italic>E</italic> <sub>2</sub> and <italic>E</italic> <sub>3</sub>. At any point, the occurrence of bifurcation of the pitch for</p> ... Show More
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Publication Date
Sat Oct 01 2016
Journal Name
I-manager’s Journal On Communication Engineering And Systems
SOLVING NETWORK CONGESTION PROBLEM BY QUALITY OF SERVICE ANALYSIS USING OPNET
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Among many problems that reduced the performance of the network, especially Wide Area Network, congestion is one of these, which is caused when traffic request reaches or exceeds the available capacity of a route, resulting in blocking and less throughput per unit time. Congestion management attributes try to manage such cases. The work presented in this paper deals with an important issue that is the Quality of Service (QoS) techniques. QoS is the combination effect on service level, which locates the user's degree of contentment of the service. In this paper, packet schedulers (FIFO, WFQ, CQ and PQ) were implemented and evaluated under different applications with different priorities. The results show that WFQ scheduler gives acceptable r

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Publication Date
Tue Mar 31 2015
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Reduction of Sulfur Compounds from Petroleum Fraction Using Oxidation-Adsorption Technique
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Oxidation of sulfur compounds in fuel followed by an adsorption process were studied using two modes of operation, batch mode and continuous mode (fixed bed). In batch experiment oxidation process of kerosene with sulfur content 2360 ppm was achieved to study the effect of amount of hydrogen peroxide(2.5, 4, 6 and 10) ml at different temperature(40, 60 and 70)°C. Also the effect of amount acetic acid was studied  at the optimal conditions of the oxidation step(4ml H2O2 and 60 °C).Besides, the role of acetic acid different temperatures(40, 60, 70) °C and 4ml H2O2, effect of reaction time(5, 30, 60, 120, 300) minutes at temperatures(40,60) °C, 4ml H2O2 and 1 mlHAC)&

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Publication Date
Wed Aug 12 2020
Journal Name
International Journal On Advanced Science, Engineering And Information Technology
Developing of a 3D Printer to Produce Parts Using Powder Metal
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Publication Date
Wed Jan 20 2021
Journal Name
Journal Of Applied Sciences And Nanotechnology
Correlation of MicroRNAs-122a Gene Expression with Diabetic for Iraqi Patients
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This study was carried out to describe the gene expression of the micro RNA 122a gene with the development of diabetes in Iraq. The difference in gene expression between patients and healthy controls was properly considered. In this study, blood was isolated from 121 individuals divided into two groups as follows: 80 samples of diabetic patients and 41 samples from a healthy control. miRNA was isolated and transformed into cDNA, and the expression of mi122a was measured by qRT-PCR. The researchers looked at the relationship between age and gender and the occurrence of diabetes, as well as how they compared to controls. When comparing the mean gene expression level (Ct) of patient groups to the corresponding Ct means in the control group, th

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Publication Date
Mon Mar 03 2014
Journal Name
Journal Of Al-nahrain University
Adsorption of Ciprofloxacin Hydrochloride from Aqueous Solution by Iraqi Porcelinaite Adsorbent
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Pharmaceuticals are widely distributed in different applications and also released into the environment. Adsorption of Ciprofloxacin HCl (CIPH) on Porcelinaite was studied at ambient conditions. The adsorption isotherms can be well described using the Freundlich and Temkin equations. The pH of the solution influences significantly the adsorption capacity of Porcelinaite, the adsorption of CIPH increased from the initial pH 1.3 and then decreased over the pH rang of 3.8-9. The adsorption is sensitive to the change in ionic Strength, which indicate that electrostatic attraction is a significant mechanism for sorption process. The enthalpy change (ΔH) for the adsorption of CIPH onto Porcelinaite signifies an endothermic adsorption. The ΔG va

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Publication Date
Wed Feb 17 2016
Journal Name
International Journal Of Computer Applications
Aerodynamic Characteristics of CLARK-Y Smoothed Inverted Wing with Ground Effects
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A two-dimensional computational study had been performed regarding aerodynamic forces and pressures affecting a cambered inverted airfoil, CLARK-Y smoothed with ground effects by solving the Reynolds-averaged Navier-Stokes equations, using the commercial software COMSOL Multiphysics 5.0 solver. Turbulence effects are modeled using the Menter shear-stress transport (SST) two-equation model. The negative lift (down-force), drag forces and pressures surface were predicted through the simulation of wings over inverted wings in different parameters namely; varying incidences i.e. angles of attack of the airfoils, varying the ride hide from the ground covering various force regions, two-dimensional cross-section of the inverted front wings to be

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Publication Date
Thu Jun 15 2023
Journal Name
Romanian Neurosurgery
Delayed intraoperative rupture of clipped aneurysm during the awaking from anaesthesia
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Introduction. Intraoperative rupture (IOR) of an aneurysm is a frightful complication that causes significant morbidity and mortality worldwide. IOR can be attributed to various parameters, including hypertension, increased intracranial pressure (ICP), fragility of the vessels, and inadequate anaesthesia. IOR due to insufficient anaesthesia is scarcely reported in the literature. Here, we describe a re-ruptured anterior communicating artery (ACoA) after incomplete clipping of the neck during craniotomy closure due to unintended early wake-up from anaesthesia with a discussion about the management. Case description. A 38-year-old male suddenly developed a severe headache, a brief loss of consciousness, and vomiting. Computed tomogr

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Publication Date
Sun Jun 07 2015
Journal Name
Baghdad Science Journal
Effect glucosamine sulfate drug on liver tissue of male Albino mice
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The current study designed to determine the effect of Glucosamine sulfate on the liver tissue of Albino mice .the study included (40)mice divided in to 4 groups(control group had distilled water orally ).The other groups treated with(1000,2000,3000)ml/k .respectively for 8 week .the liver have been taken from dissected animal for microscopic preparation to study the histological changes .Frequently histopathologicale changes appeared in the liver tissue of the exposure groups during (4-8)week .This changes depends on (Dose and Time ). The effects were Congestion ,Infiltration ,Swelling ,Vaculation ,Hyalinization , Amyloid and Necrosis.

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