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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
Sun Dec 30 2018
Journal Name
2018 Computing In Cardiology Conference (cinc)
Theoretical and Experimental Reflection Coefficients in Flexible Tubes as a Function of the Mach Number
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The standard formulation of Wave Intensity Analysis (WIA) assumes that the flow velocity (U) in the conduit is <;<; the velocity of propagation of waves (c) in the system, and Mach number, M=U/c, is negligible. However, in the large conduit arteries, U is relatively high due to ventricular contraction and c is relatively low due to the large compliance; thus M is > 0, and may not be ignored. Therefore, the aim of this study is to identify experimentally the relationship between M and the reflection coefficient in vitro. Combinations of flexible tubes, of 2 m in length with isotropic and uniform circular cross sectional area along their longitudinal axes, were used to present mother and daughter tubes to produce a range of reflection coeffic

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Publication Date
Fri Oct 28 2022
Journal Name
Political Sciences Journal
Applications of contemporary feminist theory and its role in international relations (Singapore as a Model)
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Since the emergence of the science of international relations as an independent academic scientific field,  various theories and trends have appeared and have tried to understand and explain the international reality and give a clear picture of what is happening within the international system of interactions and influences and the search for tools for stability and peace in international relations. Among these theories is the feminist theory, which is a new intellectual trend on the level of international relations theories,  which tried to give an explanation of what is happening in world politics and in international relations in particular. The main issue that feminist theory is concerned with is the lack of women’s subordination

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Publication Date
Thu Nov 01 2018
Journal Name
Al-kindy College Medical Journal
The Efficacy and Safety Of Using Hydrochlorothiazide As Adjuvant Therapy In Pediatric Urinary Tract Infections
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Background: Acute urinary tract infection is a common bacterial infection causing illness in infants and children. At age of seven, 8% of girls and 2% of boys will have at least one episode. Although drinking water and using home remedies are known to help to flush away bacteria and keeps them from sticking to the bladder wall, researches to test the efficacy and safety of hydrochlorothiazide's diuretic effect as adjuvant to the antibiotics in pediatric age groups are lacking, and so this research was to address this subject.

Objectives: To assess the effectiveness   and  the safety of hydrochlorothiazide as adjuvant therapy to the antibiotics in treating acute urinary tract infect

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Publication Date
Fri Dec 01 2017
Journal Name
Iraqi Postgraduate Medical Journal
The polycystic ovary syndrome as a cause of increase in inflammatory markers and metabolic risks
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BACKGROUND: Polycystic ovary syndrome(PCOS) is one of the most common endocrine disorder affecting women in reproductive age. No single etiologic factor fully accounts for the spectrum of abnormalities in the polycystic ovary syndrome. Different changes in hormonal, metabolism and the inflammatory markers as squealy of PCOS with adverse effect on the women life. OBJECTIVE: To study the relationship between polycystic ovary syndrome and levels of C-reactive protein, human interleukin and hormonal and metabolic alteration in women with PCOS PATIENTS AND METHODS: Thirty women with Polycystic Ovary syndrome (PCOS) and other thirty women without PCOS were included. Venous blood samples were taken in early follicular phase of menstrual cycle [day

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Publication Date
Mon Feb 21 2022
Journal Name
Научный форум: Филология, искусствоведение и культурология: сб. ст. по материалам Lvi междунар. науч.-практ. конф. – No 2 (56). – М
Comparative analysis of zoomorphic metaphors in Russian and Arabic as a method for studying linguoculturology
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: zonal are included in phraseological units, form metaphorical names for a person, give him various emotional and evaluative characteristics. This article examines the topic of zoomorphic metaphors that characterize a person in the Russian and Arabic languages in the aspect of their comparative analysis, since the comparative analysis of the metaphorical meanings of animalisms is an important method for studying cultural linguistics, since zoomorphic metaphors are a reflection of culture in a language.

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Publication Date
Tue Nov 21 2023
Journal Name
Pharmacia
A comparative study of oral diacerein and transdermal diacerein as Novasomal gel in a model of MIA induced Osteoarthritis in rats
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Background: Osteoarthritis is a chronic pathology of the joints causing disability and morbidity. Diacerein is a disease-modifying agent indicated for osteoarthritis management with enhanced performance and have much lower side effects profile than conventional non-steroidal anti-inflammatory drugs. Oral administration of Diacerein is associated with a laxative effect, thus causing treatment discontinuation. Aim: This study aimed to evaluate the activity of Diacerein novasome-based transdermal gel compared with standard oral treatment in the management of induced osteoarthritis in a rat model. Materials and methods: A single intra-articular injection of monosodium iodoacetate was administered to the left knee joint, resulting in the develop

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Publication Date
Wed Dec 18 2019
Journal Name
Baghdad Science Journal
A Modified Approach by Using Prediction to Build a Best Threshold in ARX Model with Practical Application
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The proposal of nonlinear models is one of the most important methods in time series analysis, which has a wide potential for predicting various phenomena, including physical, engineering and economic, by studying the characteristics of random disturbances in order to arrive at accurate predictions.

In this, the autoregressive model with exogenous variable was built using a threshold as the first method, using two proposed approaches that were used to determine the best cutting point of [the predictability forward (forecasting) and the predictability in the time series (prediction), through the threshold point indicator]. B-J seasonal models are used as a second method based on the principle of the two proposed approaches in dete

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Publication Date
Thu Jun 01 2017
Journal Name
Iosr Journal Of Computer Engineering
Lossy Image Compression Using Wavelet Transform, Polynomial Prediction And Block Truncation Coding
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Publication Date
Mon Sep 01 2014
Journal Name
Ibn Al-haitham Jour. For Pure & Appl. Sci
Studying the Biological Activity of Some Oxazepine Derivatives Against Some G(+) and G(-) Bacteria.
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The preliminary test of the compounds N [2– (3,4–dimethoxy nitrobenzene oxazepine– 2,3–dihydro–4,7–dione]–5–mercupto–2–amino–1,3,4–thiadiazol [A] and N [ 2–anthralidene– 5– ( 2–nitrophenyl ) –1,3–oxazepine–4,7–dione–2–d](5–mercapto–1,3,4–thiadiazole–2–amin) [B] , showed that they possess high activity against some positive and negative bacteria , like pseudomonas aeruginosa (pseudo.), Escherichia coli (E-coli), staphylococcus aureus (sta.) and Bacillus subtilis (Ba.) and finally there is a study of the effect of some antibiotics like streptomycin (S), gentamycin (GN), chloramphenicol (C) and Nalitixic acid (NA) in order to compare the differences in effects. In the present study, results

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Publication Date
Thu Oct 31 2013
Journal Name
Al-khwarizmi Engineering Journal
Simulation of a Wet Sulfuric Acid Process (WSA) for Utilization of Acid Gas Separated from Omani Natural Gas
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In this study, a proposed process for the utilization of hydrogen sulphide separated with other gases from omani natural gas for the production of sulphuric acid by wet sulphuric acid process (WSA) was studied. The processwas simulated at an acid gas feed flow of   5000 m3/hr using Aspen ONE- V7.1-HYSYS software. A sensitivity analysis was conducted to determine the optimum conditions for the operation of plant. This included primarily the threepacked bed reactors connected in series for the production of sulphur trioxidewhich represented the bottleneck of the process. The optimum feed temperature  and catalyst bed volume for each reactor were estimated and then used in the simulation of the whole process for tw

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