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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 01 2021
Journal Name
Baghdad Science Journal
Using Fuzzy Clustering to Detect the Tumor Area in Stomach Medical Images
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Although the number of stomach tumor patients reduced obviously during last decades in western countries, but this illness is still one of the main causes of death in developing countries. The aim of this research is to detect the area of a tumor in a stomach images based on fuzzy clustering. The proposed methodology consists of three stages. The stomach images are divided into four quarters and then features elicited from each quarter in the first stage by utilizing seven moments invariant. Fuzzy C-Mean clustering (FCM) was employed in the second stage for each quarter to collect the features of each quarter into clusters. Manhattan distance was calculated in the third stage among all clusters' centers in all quarters to disclosure of t

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Publication Date
Sun Oct 22 2023
Journal Name
مجلة الدراسات المستدامة
Strategies, Techniques and Activities Used by English Language Teachers in Employing Online Teaching
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Publication Date
Sat Oct 28 2023
Journal Name
Baghdad Science Journal
Synthesis and Characterization of Calcium Oxide Impregnated on Silica from Duck Egg Shells and Rice Husks as Heterogeneous Catalysts for Biodiesel Synthesis
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Biodiesel can be prepared from various types of vegetable oils or animal fats with the aid of a catalyst.
Calcium oxide (CaO) is one of the prospective heterogeneous catalysts for biodiesel synthesis. Modification
of CaO by impregnation on silica (SiO2) can improve the performance of CaO as catalyst. Egg shells and rice
husks as biomass waste can be used as raw materials for the preparation of the silica modified CaO catalyst.
The present study was directed to synthesize and characterize CaO impregnated SiO2 catalyst from biomass
waste and apply it as catalyst in biodiesel synthesis. The catalyst was synthesized by wet impregnation
method and characterized by x-ray diffraction, x-ray fluorescence, nitr

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Publication Date
Sun Sep 01 2019
Journal Name
Transylvanian Review
Metacongnitive Thinking Skills Implied in Questions and Activities of Computer Textbook for the Fifth Grade Preparatory
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The research aims to know the availability of supra-cognitive thinking skills in the questions and activities of the computer book for the fifth grade preparatory scientific and literary branches in Iraq for the academic year 2018/2019, as the researcher has prepared a list of supra-cognitive thinking skills included two areas and (6) key skills and (27) A sub - skill, where by the questions and activities of the aforementioned authors were analyzed. The researcher followed the descriptive analytical approach "method of content analysis", and adopted the explicit and implicit unit of analysis, as was verified the validity and stability of the analysis, and the results showed unevenness and imbalance in the distribution of supra-cognitive th

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Publication Date
Thu Jan 24 2019
Journal Name
Journal Of Education College Wasit University
Postmodernism and Technology in Don Delillo's Novel The White Noise
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This paper aims at investigating the effect of postmodernism and technology on the social life in Don Delillo's novel The White Noise. In this novel, Don Delillo portrays the chaotic life by using modern technology which has been presented by three ways. The first way is by television as being a source of information and entertainment. The second way is by the toxic event whereas the third is by Dylar's episode and its destructive consequences. He depicts that through the atmosphere of Jack's family plus its effects on the life and thoughts of the elders and society. He proves that technology is leading humanity not to safety, but to death. He further highlights that by showing the impact of technology on the life of the main charac

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Publication Date
Sun Jun 08 2025
Journal Name
Journal Of Natural Science, Biology And Medicine
The Value of White Blood Cells and Platelets Indices in Prediction of Tubal Ectopic Pregnancy Rupture
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Publication Date
Sun Jun 08 2025
Journal Name
J Nat Sc Biol Med
The Value of White Blood Cells and Platelets Indices in Prediction of Tubal Ectopic Pregnancy Rupture
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Scopus
Publication Date
Mon Aug 01 2016
Journal Name
Journal Of Engineering
Prediction of Monthly Fluoride Content in Tigris River using SARIMA Model in R Software
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The need to create the optimal water quality management process has motivated researchers to pursue prediction modeling development. One of the widely important forecasting models is the sessional autoregressive integrated moving average (SARIMA) model. In the present study, a SARIMA model was developed in R software to fit a time series data of monthly fluoride content collected from six stations on Tigris River for the period from 2004 to 2014. The adequate SARIMA model that has the least Akaike's information criterion (AIC) and mean squared error (MSE) was found to be SARIMA (2,0,0) (0,1,1). The model parameters were identified and diagnosed to derive the forecasting equations at each selected location. The correlation coefficien

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Publication Date
Mon Aug 01 2016
Journal Name
Journal Of Engineering
Prediction of Monthly Fluoride Content in Tigris River using SARIMA Model in R Software
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The need to create the optimal water quality management process has motivated researchers to pursue prediction modeling development. One of the widely important forecasting models is the sessional autoregressive integrated moving average (SARIMA) model. In the present study, a SARIMA model was developed in R software to fit a time series data of monthly fluoride content collected from six stations on Tigris River for the period from 2004 to 2014. The adequate SARIMA model that has the least Akaike's information criterion (AIC) and mean squared error (MSE) was found to be SARIMA (2, 0, 0) (0,1,1). The model parameters were identified and diagnosed to derive the forecasting equations at each selected location. The correlat

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Publication Date
Fri Jan 01 2016
Journal Name
Iraqi Journal Of Agricultural Sciences
Study the effect of cytokinins and auxins in the composition and production of In Vitro plantlets Hippeastrum Hybridum
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