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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
Fri Oct 01 2010
Journal Name
Iraqi Journal Of Physics
Evaluation of polyurethane and polyurethane /polyvinyl chloride blend coatings on steel as corrosion protection using EIS technique
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This paper was aimed to evaluate the polyurethane (PU) and polyurethane/polyvinyl chloride (90 wt. % / 10 wt. %) as organic coating of carbon steel substrate against marine environment (3.5 wt.% NaCl aqueous solution) as a severe corrosion environment . The electrochemical impedance spectroscopy (EIS) and fitting impedance data by ZsimpWin 3.22 software were used to estimate the physical barrier of the samples for different exposure times. Different equivalent electrical circuits were proposed for the physical barrier at different immersion times to get appropriate fitting .Both PU and PU/PVC coatings showed excellent corrosion protection ability for steel .The PU/PVC coating showed better protection and stability than PU coating against

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Publication Date
Wed May 10 2023
Journal Name
Journal Of Planner And Development
Analysis and evaluation of related factors affecting community Participation as a policy to upgrade residential slums area
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have suffered from deteriorating residential neighborhoods, poor economic, social and urban living conditions of the population and deteriorating the infrastructural and superior services. These problems were the secretions of these cities' rapid urbanization. Based on the principles of sustainable urban planning and in order to achieve adequate opportunities for the lives of the population and provide them with sustainable livelihoods, policies have emerged to upgrade along the lines of community participation and programmes to reform and develop those neighbourhoods, raise their efficiency and make them livable. Thus, the problem of research was identified "The absence of a comprehensive cognitive perception of the most prominent facto

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Publication Date
Mon Jun 01 2015
Journal Name
Journal Of The College Of Languages (jcl)
Emotions conflict In Balzac’s novel The Father Goriot And Stendhal’s The Red and The Black
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Au XIXe siècle, avec l’excès de la passion, le roman français commence à avoir de nouvelles figures. Il tend à être un reflet de la pensée et de la passion. Stendhal et Balzac révèlent ainsi le conflit de l’âme et donnent à leur héros l’impression que tout est permis.

                Ces protagonistes doivent, d’une part, subir des fluctuations psychologiques, et d’autre part, ces héros doivent être capables de faire face aux rancunes et aux conflits destructeurs. Les personnages stendhaliens et balzaciens finissent par croire que leur combat ne portera pas ses fruits, parce que toute passion déséquilibrée mènera, soit à la fol

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Publication Date
Sun Jan 21 2018
Journal Name
Drug Invention Today
Preparation and evaluation of lornoxicam in situ gelling liquid suppository
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Publication Date
Sun Jul 17 2022
Journal Name
Pharmacy Education
Students' experience and evaluation of community pharmacy internship in Iraq
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Background: Pharmacy internship programmes are driven by most developed countries to outweigh the ongoing growth in the pharmacy career which encourages pharmacists to play a significant role as healthcare providers.    Objectives: This study examines pharmacy students' perception, satisfaction, challenges, and limitations with the internship curriculum.    Method: A cross-sectional study was conducted using an online survey with different elements to examine students' perceptions of various aspects.    Result: Most students reported a positive impression regarding their internships, however, they were less satisfied with the allowance for filling prescriptions and compounding also, the college's follow-up was inadequate. F

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Publication Date
Sun Oct 15 2023
Journal Name
Revista Bionatura
Estimation of amino acid concentrations in the kidney of albino mice embryo
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Amino acids are the basic building block for peptides and proteins. They are raw materials for generating hormones, purines, pyrimidines and vitamins. Amino acids also provide the body with energy through their carbon structures. The study analyzed the amino acid in the kidneys of the albino mice embryo at 17 and 19 gestation days, using a high-performance liquid chromatography device (HPLC). Samples were obtained after removing them from the embryo and placing them in an ice bath to prevent cell lysis and acid loss. The study found 18 amino acids in the kidneys of the albino mice embryo. They are Asparagine (Asn), Glutamine (Glu), Serine (Ser), Glycine (Gly), Threonine (Thr), Histidine (His), Cysteine (Cys), Alanine (Ala), Proline

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Publication Date
Tue Dec 20 2016
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
Development Accounting Rule disclosure by accounting policies in the light of Islamic and electronic banking Activities (Proposal pattern): Proposal pattern
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the bank sect for any country  is very important  because  its represent a major  nerve   to feed a verity economic and finance activities .development any state measure by development  banking  sets and its represent  important  factor to investors attract . and because  important  of this subject ,teen accounting rule is a specialized for it .its related by  Disclosures in the Financial Statements Of Banks and The Similar Institutions, its accredit  by auditing and accounting standard  consul in republic of Iraq.in date 10/28/1998.                      &

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Publication Date
Thu Aug 13 2020
Journal Name
Asia Pacific Journal Of Molecular Biology And Biotechnology
The anticancer molecular mechanism of Carnosol in human cervical cancer cells: An in vitro study
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Carnosol, a phenolic diterpene, is one of the effective anticancer agents naturally occurring in rosemary, sage, parsley, and oregano. The chemoresistance problem increased with the routinely used chemotherapy. Therefore, the efforts to find a substitute with safe and low cost have become crucial worldwide. The current study attempts to inspect the anticancer molecular mechanisms of Carnosol on modulating up- and down- regulation of multiple genetic carcinogenesis pathways. The cytotoxicity of Carnosol on Hela cells was evaluated by MTS assay. Flow cytometry was used to assess apoptosis and cell cycle arrest. The apoptotic morphological changes were obvious by dual apoptosis assay. The differential gene expression after treatment wi

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Publication Date
Thu Feb 05 2026
Journal Name
Journal Of Baghdad College Of Dentistry
An Antimicrobial Activity of Moringa Oleifera Extract in Comparison to Chlorhexidene Gluconate (In vitro study)
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Background: Oral diseases persist to be a major health problem all over the world. Various bacteria and fungi are found to be the possible pathogensresponsible for the oral diseases. Moringa oleifera it is an extraordinary nutritious vegetable tree with many different uses. These leaves have high medicinal value. In the present study, antibacterial and antifungal activities of aqueous extracts of plant Moringa oleifera in comparison to chlorohexidene gluconate and deionized water were determined. Materials and methods: The leaves of plant of Moringa oleifera were collected from College of Pharmacy; Baghdad, Iraq. Tested microorganism (bacterial and fungal) was isolated from different clinical specimens. In-vitroantimicrobial activity was pe

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Publication Date
Sun May 01 2022
Journal Name
Songklanakarin J. Sci. Technol.
Molecular identification of three novel species of Ganoderma from different habitats in Mosul, Iraq
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Reishi Mushroom, Ganoderma, is considered one of important wood-decaying medicinal mushrooms. This study aimed to identify three samples of this genus in Mosul city in February and April 2019. Three species of Ganoderma were collected from three various trees including Eucalyptus, Morus, and Olea (olive) in Mosul City, Northern Iraq. Their identifications and their DNA sequences were genetically identified by using PCR techniques according to detect nuclear ribosomal internal transcribed spacer (ITS) regions. Results exhibited the finding of Ganoderma resinaceum, Ganoderma applanatum, and Ganoderma sp. This study is first attempt to identify Reishi Mushroom by molecular methods in Iraq. Thus, the current study is considered new good d

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