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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 Aug 11 2021
Journal Name
Nauchforum
ROLE OF METAPHOR IN PUPPET IMPLEMENTATION (ON THE EXAMPLE OF D. RUBINA'S NOVEL «PETRUSHKA'S SYNDROME»)
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The article examines metaphors as one of the fundamental means used by D. Rubina when writing the novel “Parsley Syndrome” to form images of dolls as equal heroes of the work. The author of the article continues research related to the work of Dina Ilinichna Rubina, a representative of modern Russian prose.

Publication Date
Fri Dec 27 2024
Journal Name
International Journal Of Design & Nature And Ecodynamics
Amino Acid and Hormonal Profiling of the Adrenal Gland in the Pin-Tailed Sandgrouse (Pterocles alchata)
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Publication Date
Sun Dec 25 2022
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Quantitative Determination and Cytotoxic Effect of Oleanolic Acid from Olea europaea Leaves Extract Cultivated in Iraq
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Since its first description as a cytotoxic agent, Olea europaea leaves extract gained significant popularity against human breast cancer, ethyl acetate extract of Olea europaea leaves obtained by acid hydrolysis method was evaluated in vitro as cytotoxic agent against new human breast cancer (AMJ13) cell line, using the MTT assay. One main pentacyclic triterpenoid; oleanolic acid, was isolated from leaves of Olea europaea by well-known two different methods, but not used for this compound before, the acidic hydrolysis method and basic acidic method. The presence of oleanolic acid was proved in both methods with qualitative and quantitative d

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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
Fri Nov 21 2025
Journal Name
Journal Of Baghdad College Of Dentistry
The effects of different concentrations of Alum solutions on Mutans streptococci (in vitro study)
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Background: Alum has been used as a treatment medication in cases of oral and gingival ulcers, and also as antiseptic mouthwash. This study aimed to examine the effects of different concentrations of Alum on inhibition zone, viability counts and adherence ability of Mutans streptococci compared with deionized water and chlorhexidine gluconate in vitro. Materials and methods: The study dealt with an in vitro study to establish a concentration of Alum mouthrinse that would have the minimum inhibitory concentration and minimum bacteriocidal concentration. The second part evaluated the anti-adherence ability of the experimental agents. Results: This study found that the antibacterial effect of Alum increases with its concentration from 50 to 1

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Publication Date
Wed Apr 01 2020
Journal Name
Brazilian Dental Journal
In Vitro Homeostasis of Rat Oral Epithelial Cell Cultures Following Withdrawal of Periodontal Pathogens
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Abstract Inflammation of periodontal tissues is the consequence of interaction between periodontal pathogens and immune system. This is associated with increased expression of inflammatory cytokines, which may exert destructive effect to the periodontal tissues when released over long period. The aim of this study was to chronologically track the homeostasis of oral keratinocytes following removal of periodontal pathogens. This was done by investigating expression of selected inflammatory markers and integrity of epithelial monolayers in vitro. Rat oral keratinocytes were stimulated with heat-killed Fusobacterium nucleatum and Porphyromonas gingivalis over 7-days then bacteria were washed away and epithelial cells re-cultured for 3-

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Publication Date
Fri Sep 30 2022
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
Evaluation of direct withholding tax procedures as a tool to increase tax proceeds : applied research in the General Tax Authority / Direct Deduction Department
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The research aims to evaluate the direct deduction department’s procedures for the process of collecting income tax using the direct deduction method for state departments and the public sector in light of direct deduction tax instructions No. (1) of 2007 and Income Tax Law No. (113) of 1982 (amended) through Giving a clear idea of ​​the reality of tax collection procedures because this type of tax is one of great importance because it contributes to the provision of financial revenues to the state to finance its expenses and direct the economy towards achieving its social, economic and political goals. The researcher makes comparisons between the procedures of the General Tax Authority in collecting the tax and what was approved b

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Publication Date
Fri May 02 2014
Journal Name
International Journal Of Scientific & Technology Research
Synthesis, Structure And Characterization Of Zns Qds And Using It In Photocatalytic Reaction
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ZnS nanoparticles were prepared by a simple microwave irradiation method under mild condition. The starting materials for the synthesis of ZnS quantum dots were zinc acetate (R & M Chemical) as zinc source, thioacetamide as a sulfur source and ethylene glycol as a solvent. All chemicals were analytical grade products and used without further purification. The quantum dots of ZnS with cubic structure were characterized by X-ray powder diffraction (XRD), the morphology of the film is seen by scanning electron microscopy (SEM). The particle size is determined by field effect scanning electron microscopy (FESEM), UV-Visible absorption spectroscopy and XRD. UV-Visible absorption spectroscopy analysis shows that the absorption peak of the as-prep

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Publication Date
Wed Jan 01 2020
Journal Name
Annals Of Tropical Medicine And Public Health
Synthesis and characterization of new phthalimide with 6- mercaptopurine or 2- aminothiazole conjugate used dithiocarbamate spacer as anticancer agents
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Publication Date
Sun Dec 30 2012
Journal Name
Al-kindy College Medical Journal
Evaluation of Medication Errors in Hospitalized Patients
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Objectives: Many medication errors occur in the hospital, and these can endanger patients. The purpose of this study was to evaluate the incidence of medication errors in hospitalized patients, and to categorize the most frequent types of errors, and to asses the possible measures that may prevent the occurrence of such errors.
Methods: A prospective, exploratory, and evaluative study, using direct observation method to detect medication errors in adult hospitalized patients in medical and surgical units in Baquba Teaching Hospital- Diyala-Iraq.. The files of 299 patients had been reviewed from July 2009 to September 2009, including medication orders and treatment sheets to detect existing errors. The detected errors were recorded and

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