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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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Wed Jan 01 2025
Journal Name
Advances In Animal And Veterinary Sciences
Exposure to Environmental Perfluorooctanoic Acid (PFOA) Induced Hepatocellular Apoptosis and Alteration in Serum Biomarkers in Diabetic Guinea Pigs
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Publication Date
Mon Sep 05 2016
Journal Name
Iraqi Journal Of Market Research And Consumer Protection
EVALUATION OF CHEMICAL AND MICROBIAL QUALITY FOR SOME BOTTLED WATER THAT AVAIABLE IN LOCAL MARKETS: EVALUATION OF CHEMICAL AND MICROBIAL QUALITY FOR SOME BOTTLED WATER THAT AVAIABLE IN LOCAL MARKETS
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This study was conducted to evaluate the bottled water quality for the six-producing companies in Baghdad city, where selected six brands which are the most marketed in the Iraqi market, especially in Baghdad, where taking the proper amount of bottled water in September 2015 and included the studied characteristics (EC , pH ,TDS, Turbidity, Ca+2, Mg+2, Cl-, No3-, So4-2, HCO3-, Na+ and K+) in addition to the total population of bacteria aerobic and coliform, and compare the results with the standard specifications of the Iraqi and the World Health Organization (WHO), as well as to compare the results of sampling specifications mentioned on the packaging by the producing companies. The results showed the presence of high significant differ

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Fri Sep 01 2017
Journal Name
Pak. J. Pharm. Sci.
Moxifloxacin reduces stenotrophomonas maltophilia adhesion to mouse intestinal tract in vitro
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Publication Date
Wed Mar 01 2023
Journal Name
Al-khwarizmi Engineering Journal
Succinic acid Production Strategy: Raw material, Organisms and Recent Applications in pharmaceutical and Food: Critical Review
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Succinic acid is an essential base ingredient for manufacturing various industrial chemicals. Succinic acid has been acknowledged as one of the most significant bio based building block chemicals. Rapid demand for succinic acid has been noticed in the last 10 years. The production methods and mechanisms developed. Hence, these techniques and operations need to be revised. Recently, an omnibus rule for developing succinic acid is to find renewable carbohydrate Feedstocks. The sustainability of the resource is crucial to disintegrate the massive use of petroleum based-production. Accordingly, systematically reviewing the latest findings of bacterial production and related fermentation methods is critical. Therefore, this paper aims to stud

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Publication Date
Tue Dec 22 2020
Journal Name
Lecture Notes In Civil Engineering
Geometric Nonlinear Synthetic Earthquake Analysis of Base Isolated Tall Steel Buildings Under Site-Specific Seismic Loading
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Publication Date
Mon Feb 04 2019
Journal Name
Iraqi Journal Of Physics
Risks assessment for the retrieval of radioactive waste from the old Russian cemetery Al -Tuwaitha site
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In this work the radioactive wastes in the Old Russian
Cemetery Al -Tuwaitha site were classified according to risks for
workers who are involved in the retrieval process. The exposure
assessment results expressed as estimates of radionuclide intakes by
inhalation and ingestion, exposure rates and duration for external
exposure pathways, and committed effective dose equivalents to
individuals from all relevant radionuclides and pathways. Results
showed the presence of natural radionuclides Ra-226, Th-234 and K-
40, as well as the produced radionuclide Cs-137 and Eu-152 in the
cemetery wells. The absorbed doses from the waste were classified to
two categories; exempt waste and low level waste according to

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Publication Date
Fri Mar 10 2023
Journal Name
Journal Of Namibian Studies : History Politics Culture
The Sufi influence in the Iraqi novel, the Lamia, is a model
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In our research, we seek to shed a light on one of the most important and sensitive issues, namely, the Sufi influence in the Iraqi novel through the lame maqam of the novelist Jumaa Al-Lami, the Sufi discourse contains many semantic paradoxes between the text's apparent pronunciation and its interpretation of the format and the context that produced these patterns, and incited them, which concludes different results from the prevailing provisions and fixed ideas from the narrative text.The Arabic and Iraqi novel in particular became inspired by the power of Sufi discourse by talking about several Sufi figures by referring to it openly, or implicitly inspired by unauthorized concealment, in employing some of the ideas, or summoning

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Publication Date
Thu Dec 31 2020
Journal Name
College Of Islamic Sciences
The cultural identity in the novel "The American Granddaughter" by writer InamKaghi
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The identity of the cultural identity of the party (the ego and the other) during a series of questions subject to the transformations of history and the process of culture, the search of identity and its characteristics within the novel discourse calls to address the cultural impact communication discourse aims to reveal the functional and intellectual benefits that contributed to the formation of cultural identity, and stand at the most important manifestations And the secretions that mimic a world remains part of it present in the imagination of the producer of the text is moving in accordance with the holistic perception of the world embedded between the lines of the trial.The question of identity as an intellectual dimension in orde

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Publication Date
Tue Mar 29 2022
Journal Name
Journal Of The Mechanical Behavior Of Materials
Prediction of bearing capacity of driven piles for Basrah governatore using SPT and MATLAB
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Based on the results of standard penetration tests (SPTs) conducted in Al-Basrah governorate, this research aims to present thematic maps and equations for estimating the bearing capacity of driven piles having several lengths. The work includes drilling 135 boreholes to a depth of 10 m below the existing ground level and three standard penetration tests (SPT) at depths of 1.5, 6, and 9.5 m were conducted in each borehole. MATLAB software and corrected SPT values were used to determine the bearing capacity of driven piles in Al-Basrah. Several-order interpolation polynomials are suggested to estimate the bearing capacity of driven piles, but the first-order polynomial is considered the most straightforward. Furthermore, the root means squar

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Publication Date
Mon Jan 01 2018
Journal Name
Communications In Computer And Information Science
Automatically Recognizing Emotions in Text Using Prediction by Partial Matching (PPM) Text Compression Method
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In this paper, we investigate the automatic recognition of emotion in text. We perform experiments with a new method of classification based on the PPM character-based text compression scheme. These experiments involve both coarse-grained classification (whether a text is emotional or not) and also fine-grained classification such as recognising Ekman’s six basic emotions (Anger, Disgust, Fear, Happiness, Sadness, Surprise). Experimental results with three datasets show that the new method significantly outperforms the traditional word-based text classification methods. The results show that the PPM compression based classification method is able to distinguish between emotional and nonemotional text with high accuracy, between texts invo

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