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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 Sep 14 2016
Journal Name
Journal Of Baghdad College Of Dentistry
Immunohistochemical Expression of MMP2, VEGF and D2-40 as Biological Markers of Local Invasion Potential, Angiogenesis and Lymphangiogenesis in Oral Squamous Cell Carcinoma and Verrucous Carcinoma
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Background: Verrucous carcinoma (VSCC) is considered as a rare well differentiated carcinoma variant of SCC with no metastatic potential. The aim of this study is to evaluate the Immunohistochemical expression MMP-2, VEGF and D2-40 expression in OSCC and VSCC. Materials and methods: Thirty formalin fixed paraffin embedded tissue blocks of OSCC and another twelve VSCC were collected and Four micrometer thick sections were cut from each block and mounted on positively charged slides and stained immunohistochemically with monoclonal antibodies to MMP-2, VEGF and D2-40. Results: there is no statistical difference between SCC and VSCC regarding the immunoexpression of MMP-2 and VEGF. While the lymphatic vessels density were higher in SCC than V

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Publication Date
Wed Dec 15 2021
Journal Name
Al-academy
The communicative education of fine arts in the COVID-19 crisis and its manifestations in the modernization of the works of the Iraqi painter "Nabil Ali as a model"
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 This study attempts to address the importance of communicative digitization in the field of various arts for the sake of continuity of shopping and aesthetic, artistic and intellectual appreciation of artistic achievements by the recipient on various places of their residence in light of the COVID 19 crisis, and to highlight the importance of the plastic arts of the Iraqi painter exclusively and how it expresses in a contemporary way the environment or life reality in Iraq in light of this crisis. With all its implications affecting the life reality from various aspects and methods of its negative and positive employment. As for the research procedures, the researcher reviewed the research methodology represented by the descriptive ana

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Publication Date
Thu Dec 29 2022
Journal Name
Journal Of The College Of Languages (jcl)
The morphological structure of nouns and verbs in the novel "Astonishment" by the novelist Aharon Applefield, Morphological study.: מבנה שמות עצם והפעלים ברומן תימהון לסופר אהרון אפלפלד עיון מורפולוגי
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This research sheds light on the morphological structure of nouns and verbs in the novel "ASTONISHMENT" by the novelist Aharon Applefield by analysing selected models from the novel in a morphological analysis in order to identify the most important morphological features of this structure according to a statistical analytical approach.

 The morphological structure is the main pillar of the linguistic structure of the literary text. Morphology is the science that studies the word, by which its structure and original letters are known, and the change that has occurred to it.  The aesthetics of the fictional text is reflected in this structure, through which the writer conveys his ideas and narrations to the reader.  The research

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Publication Date
Sun Dec 31 2023
Journal Name
Lark
Digital and pedagogical practices of French as a foreign language in a post-COVID-19 context (The case of the University of Baghdad)
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Publication Date
Fri Apr 30 2021
Journal Name
Egyptian Journal Of Chemistry
Indirect Spectrophotometric Determination of Mebendazole Using NBromosuccinimide as An Oxidant and Tartarazine Dye as Analytical Reagent
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A simple indirect spectrophotometric method for determination of mebendazol in pure and pharmaceutical formulation was presented in this study. UV-Visible spectrophotometry using the optimal conditions was developed for determination of mebendazole in pure drug and different preparation samples. The method is based on the oxidation of drug by nbromosuccinimide with hydrochloric acid and the left amount of oxidizing agent was determined by the reaction with tartarazine and the absorbance was measured at 428 nm. Calibration curves were linear in the range of 5 to 30 µg.mL-1 with molar absorptivity 8437.2 L.mol-1 .cm-1 . The limits of detection and quantification were determined and found to be 0.7770 µg.mL-1 and 2.3400 µg.mL-1 respec

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Publication Date
Sun Apr 25 2021
Journal Name
Egyptian Journal Of Chemistry
Indirect spectrophotometric determination of Mebendazole using n-bromosuccinimide as an oxidant and tartarazine dye as analytical reagent
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Publication Date
Thu Jun 15 2023
Journal Name
Journal Of Baghdad College Of Dentistry
Antibacterial and cytotoxic effect of a novel bio-logical Nano-silver fluoride synthesized from moringa oleifera leaf extract
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Background: A great dental and biomedical interest had been paid to silver nanoparticles because of their antimicrobial activity. Objective: To evaluate the antimicrobial and cytotoxic activity of a newly developed Nano-silver fluoride that was synthesized from moringa oleifera leaf extract against S. mutants.  Material and method: The green synthesis method was used to prepare Nano-silver fluoride from moringa oleifera leaf extract. The minimum inhibitory concentration and the minimum bactericidal concentration were evaluated using brain heart infusion plates, while the cytotoxicity was evaluated by the hemolytic activity. Results: Nano-silver fluoride had a bactericidal and bacteriostatic effect (MIC was 60 ppm a

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Publication Date
Wed May 01 2019
Journal Name
Sensors And Actuators B: Chemical
Fabrication and Characterizations of a Novel Etched-tapered Single Mode Optical Fiber Ammonia Sensors Integrating PANI/GNF Nanocomposite
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Publication Date
Wed Mar 10 2021
Journal Name
Baghdad Science Journal
synthesis and studies of mixed-Ligand complexes of some transition Elements
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I've been in this work to prepare some complexes containing mixed Kandat with some transitional elements which new complexes according to the best of our knowledge and to refer to the information from the Internet until I have been studying this diagnosis Aalmakdat

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Publication Date
Wed Mar 29 2023
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Cold Cracking Technology for Crude Oil Upgrading in Qaiyarah Heavy Oil Field; Technical and Economical Evaluation
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Heavy oil is classified as unconventional oil resource because of its difficulty to recover in its natural state, difficulties in transport and difficulties in marketing it. Upgrading solution to the heavy oil has positive impact technically and economically specially when it will be a competitive with conventional oils from the marketing prospective. Developing Qaiyarah heavy oil field was neglected in the last five decades, the main reason was due to the low quality of the crude oil resulted in the high viscosity and density of the crude oil in the field which was and still a major challenge putting them on the major stream line of production in Iraq. The low quality of the crude properties led to lower oil prices in the global markets

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