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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 Sep 22 2019
Journal Name
Baghdad Science Journal
The Antibacterial, Antiheamolytic, and Antioxidant Activities of Laurus nobilis and Alhagi maurorum Native to Iraq.
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Ethanolic crude extracts of leaves from Laurus nobilis and Alhagi maurorumfor were screened for alkaloids, saponins, tannins, anthraquinones, steroids, flavonoids, glycosides, and glucosides contents. Biochemical activities, including antibacterial activity, antioxidant, and antihemolytic activity, were investigated. Antibacterial activity against Three types of pathogenic bacteria was detected by disc diffusion analysis and characterized by zone of inhibition (ZOI). Antioxidant properties were determined by a diphenyl-1- picrylhydrazyl (DPPH) method. Results revealed that the inhibitory activity of the plants against G+ve and G-ve bacteria were different, where the greatest ZOI  of  Alhagi maurorum a

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Publication Date
Sun Jun 11 1989
Journal Name
مجلة متحف التاريخ الطبيعي
The Role of Specific Amino Acids in the Protection of Escherichia coli Against B-Lactam Antibiotics In Vitro
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ABSTRACT The role of specific amino acids namely cysteine, methionine, threonine and asparagine in the protection provided by vamin solution against B-lactam inhibition to E. coli was evaluated in vitro. In minimal medium, Cells were treated with 32 ug/ml of penicillin G, carbencillin, hostacillin, cloxacillin and cephalotin in the presence of specific amino acid supplementations. Deletion of specific amino acids from the media abolished the protection provided by vamin. Threonine was essential for the protection of cells against all tested antibiotics, while cysteine was essential for protection against carbencillin and cephalotin Deletion of methionine or asparagine abolished the protec- tion against carbencillin and to a less extent ce

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Publication Date
Mon Jan 01 2018
Journal Name
The Journal Of Contemporary Dental Practice
Assessment of Ions released from Three Types of Orthodontic Brackets immersed in Different Mouthwashes: An in vitro Study
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Publication Date
Sun Jul 01 1990
Journal Name
Bulletin Of The Iraq Natural History Museum (p-issn: 1017-8678 , E-issn: 2311-9799)
THE ROLE OF SPECIFIC AMINO ACIDS IN THE PROTECTION OF E. COLI AGAINST B-LACTAM ANTIBIOTICS IN VITRO
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The role of specific amino acids namely cysteine, methionine, threonine and asparagine in the protection provided by vamin solution against B-lactam inhibition to E. coli was evaluated in vitro In minimal medium, cells were treated with 32 ug/ml of penicillin G, carbenciLlin, hostacillin, cloxacillin and cephalotin in the presence of specific amino acid supplementation. Deletion of specific amino acids from the media abolished the protection provided by vamin. Threonine was essential for the protection of cells against all tested antibiotics, while cysteine was essential for protection against carbencillin and sephalotin. Deletion of methionine or asparagine abolished the protection against carbencillin and to a less extent cephalotin.

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Publication Date
Tue Feb 01 2022
Journal Name
Baghdad Science Journal
Milk Tumor Necrosis Factor Alpha and Interleukin-1Beta Among Toxoplasma gondii-Free and Infected Women
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Pro-inflammatory cytokines play an important role in intercellular communications. In the last two decades, many cytokines have been identified in human milk. These cytokines are variable according to different conditions such as pathogenic infections which strongly stimulated the immune response. The present study aims to determine of IL1β and TNF-α in Toxoplasma gondii-free and infected women in an attempt to clarify the impacts of the infections on cytokines especially in mother's milk. The serum and milk sample were collected from 96 samples (48 for seropositive and 48 for seronegative). To confirm the Toxoplasma gondii infection; enzyme linked immunofluorescence assay (ELIFA) was used to detect anti-Toxoplasma Ig

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Publication Date
Fri Aug 19 2022
Journal Name
International Journal Of Health Sciences
Interleukin-32, interleukin-33 and acid phosphatase levels in patients with Helicobacter Pylori
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The study was carried out to detection of H. pylori in (218) patients who attended two teaching hospitals in Baghdad. The diagnosis was done by Immunochromatography methods. Stools and blood samples were taken from each patient as well as other (30) healthy control matching in age. The study included measurement the Levels of Interleukin-32, Interleukin-33, and Acid phosphatase   in sera of patients and control .The result indicated  presence  of H pylori antigen in 115 cases 59 cases  of males and 51 of females , Also, the result indicated  increasing levels of IL-32 and IL-33 and Acid phosphatase  in patients sera  in comparison with healthy control.

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Publication Date
Wed Apr 06 2022
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
Management using the Six Sigma approach to cost rationalization of activities : Application in the Iraqi mechanical carpet factory
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The textile industries play a prominent role in reviving the national economy, but they are currently suffering from several problems, including the high costs of their activities, the low quality of their production processes, and accordingly, the hexagonal diffraction approach came to help analyze production activities to determine which of them are the most expensive and do not have a benefit or cost greater than Its benefit as a result of waste and losses that accompany its implementation. And by applying to the Iraqi mechanical carpet factory, the research reached several conclusions, the most important of which is the presence of several sources of waste and loss, such as activities and operations that do not add value, whi

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Publication Date
Tue Feb 19 2019
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
The role of Islamic banks to attract savings to funding banking activities in Iraq For period (2008-2012)
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Islamic banks are a financial institution that is interested in attracting financial savings from financial entities and directing them towards those with financial deficits, both for consumption purposes or for investment purposes. It provides banking services provided by commercial banks and other services But based on the principles and principles of Islamic law, and because of its recent emergence in Iraq, its ability to attract savings is not like non-Islamic commercial banks, which puts them in the option of using their capital to achieve its objective of banking. The research started from the premise that "Islamic banks in Iraq during the period (2008-2012) rely on their capital to perform their activities more than they rely on d

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Publication Date
Fri Dec 15 2023
Journal Name
Bionatura
Evaluation of the Drinking water in some Hospitals in Baghdad
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Due to the significance of hospital drinking water, a study was done to assess the water in three hospitals in Baghdad (Al-Yarmouk Teaching Hospital, Ibn Sina Hospital, and Ibn-Al-Nafis Hospital) for its nature and quality, compare it to other hospitals in terms of its physical, chemical, and bacterial specifications, and compare it to international standards. According to Iraqi standards from 2009 and WHO standards from 2011, Chemical factors were measured, which included pH, Total Dissolved Solids (TDS), and Calcium Ion (Ca+2). Reported readings are all within acceptable ranges for drinking water. In contrast, turbidity, total hardness (T.H.), chlorides (Cl-), magnesium (Mg+2), the number of aerobic plates (APC), total coliform (T

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Publication Date
Sun Jan 01 2023
Journal Name
Materials Today: Proceedings
Preparation, characterization and preliminary cytotoxic evaluation of 6-mercaptopurine-coated biotinylated carbon dots nanoparticles as a drug delivery system
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