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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 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
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
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
Tue Sep 01 2009
Journal Name
Journal Of Economics And Administrative Sciences
Impact of budget on the basis of activities in the implementation of competitive strategiesApplied Study in the General Company for Electrical Industries - Tammuz Laboratory
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The Contemporary Business Environment is Surrounded by many quick and continues variable and changes which has an effect on the economic units. These variables and changes like the high competition which need many tools to help them to continue and achieve The critical success. So to achieve this they have many competitive strategies like cost leadership strategy, differentiation strategy and focus strategy.

Budget is regarded one of main tools to execute objectives polices and programs of the economic units, beside show how the economic units had execute the available economic resources.

Activity based on budgeting is regarded one of the modern technique in the m

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Publication Date
Tue Sep 24 2024
Journal Name
Arab World English Journal
A Critical Discourse Analysis of Women’s Representation in Maysaloon Hadi’s Novel The Black Eyes
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This study applies a discourse analysis framework to explore the portrayal of women in Maysloon Hadi’s novel (The Black Eyes) (2011), using Critical Discourse Analysis (CDA) and Norman Fairclough’s tri-dimensional model (1989) as the analytical foundation. It investigates the roles and challenges women face in the novel. While there is growing interest in the portrayal of women in literature, Iraqi literature—especially from the perspective of Iraqi women writers remains underexplored. Hadi’s *The Black Eyes* provides a unique case to examine this intersection. Despite the novel’s rich narrative, which offers insight into Iraqi women’s lives, there is a lack of comprehensive CDA to understand how its language constructs

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Publication Date
Thu Dec 31 2020
Journal Name
Iraqi Journal Of Market Research And Consumer Protection
EVALUATING THE QUALITY OF IMPORTED AND LOCAL FLOUR IN TERMS OF QUALITY WITH IRON AND FOLIC ACID AND ITS COMPLIANCE WITH IRAQI STANDARD: EVALUATING THE QUALITY OF IMPORTED AND LOCAL FLOUR IN TERMS OF QUALITY WITH IRON AND FOLIC ACID AND ITS COMPLIANCE WITH IRAQI STANDARD
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Food fortification has an important and necessary role in compensating for the shortage of nutritional micronutrients, especially in developing and least developed countries. So, 12 samples of flour available in the local market, whether imported or locally produced flour, were obtained during 2019. The amount of base metal of the necessary iron element in the flour models studied which are available in local markets, measured by spot testing and was compared with the values ​​that should be added according to the specification Iraqi standard. Results revealed the qualitative evaluation of iron in locally produced flour does not conform to the Iraqi standard and is almost free of any reinforcement. While the percentage of imp

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Publication Date
Sun Oct 21 2018
Journal Name
Journal Of The Faculty Of Medicine Baghdad
Thrombocytosis and CA125 as Predictor of Malignancy in Gynaecological Pelvic Mass
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Background: Pelvic masses are common in women & can present at any age of woman life, it could be benign or malignant mass and may originate from gynecological organs like cervix, uterus, uterine adnexia, or from other pelvic organs like intestine, bladder, ureters, skeletal muscle, and bone.Objective: We attempted to determine the increasing of platelet counts(> 450.000 /micro liter) and CA125serum level (> 35 U/mL) as useful tools for predicting and confirming malignancy in gynecological pelvic mass.Patients and methods: A prospective unmatched hospital based case-control study carried out at Baghdad Teaching Hospital, about 126 women were enrolled in our study, divided into two groups 60 women were control group (free o

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Publication Date
Fri Jun 28 2024
Journal Name
Curr Pharm Des
Synthesis, Characterization, and Antimicrobial Evaluation of Schiff base-mixed Ligand Complexes with Divalent Metal Ions Derived from Amoxicillin and Vanillin/Nicotinamide
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Publication Date
Wed Dec 22 2021
Journal Name
Antibiotics
Classic vs. Novel Antibacterial Approaches for Eradicating Dental Biofilm as Adjunct to Periodontal Debridement: An Evidence-Based Overview
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Periodontitis is a multifactorial chronic inflammatory disease that affects tooth-supporting soft/hard tissues of the dentition. The dental plaque biofilm is considered as a primary etiological factor in susceptible patients; however, other factors contribute to progression, such as diabetes and smoking. Current management utilizes mechanical biofilm removal as the gold standard of treatment. Antibacterial agents might be indicated in certain conditions as an adjunct to this mechanical approach. However, in view of the growing concern about bacterial resistance, alternative approaches have been investigated. Currently, a range of antimicrobial agents and protocols have been used in clinical management, but these remain largely non-v

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Publication Date
Tue Sep 10 2019
Journal Name
Periodicals Of Engineering And Natural Sciences (pen)
A classification model on tumor cancer disease based mutual information and firefly algorithm
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