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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 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
Mon Jun 27 2022
Journal Name
Sustainability
Thermal Properties of Hydrated Lime-Modified Asphalt Concrete and Modelling Evaluation for Their Effect on the Constructed Pavements in Service
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Flexible pavements are subjected to three main distress types: fatigue crack, thermal crack, and permanent deformation. Under severe climate conditions, thermal cracking particularly contributes largely to a considerable scale of premature deterioration of pavement infrastructure worldwide. This challenge is especially relevant for Europe, as weather conditions vary significantly throughout the year. Hydrated lime (HL) has been recognized as an effective additive to improve the mechanical properties of asphalt concrete for pavement applications. Previous research has found that a replacement of conventional limestone dust filler using hydrated lime at 2.5% of the total weight of aggregates generated an optimum improvement in the mec

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Publication Date
Sun Nov 01 2015
Journal Name
Journal Of Craniofacial Surgery
Evaluation of the Trephine Method in Harvesting Bone Graft From the Anterior Iliac Crest for Oral and Maxillofacial Reconstructive Surgery
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Publication Date
Wed Jul 05 2017
Journal Name
Https://www.researchgate.net/journal/international-journal-of-science-and-research-ijsr-2319-7064
Evaluation of Water Quality using Bhargava Water Quality Index Method and GIS, Case Study: Euphrates River in Al-Najaf City
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Publication Date
Tue Jun 15 2021
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Synthesis of Mutual Prodrugs of Secnidazole and Ciprofloxacin and study Their Physicochemical Properties
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  Secnidazole was linked with ciprofloxacin as mutual prodrugs to get antibiotics with broader spectrum of activity, improved physicochemical properties and given by single dose to improve patient’s compliance. Furthermore, they provide structural modifications to overcome bacterial adaptation. The structures of the synthesized compounds were confirmed using FT-IR, mass spectrometry, elemental microanalysis (CHNO) and some physiochemical properties. This modification was led to an increase in Log P values for Mutual I (Log P 1.114) and Mutual II (Log P 1.97) compared with its values for Secnidazole (Log P -0.373) and ciprofloxacin (Log P -0.832). The solubility of prodrugs had been determined in different media, Mutual II showed 1

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Publication Date
Fri Jun 07 2024
Journal Name
Medicine
Impact of TYMS gene polymorphism on the outcome of methotrexate treatment in a sample of Iraqi rheumatoid arthritis patients – identification of novel single nucleotide polymorphism: Cross-sectional study
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The current work aims to evaluate the association between genetic mutations in thymidylate synthetase (TYMS gene in exon1 and partial regions of promotor and intron 1 [877 bp, 657,220–658,096 bp]) and the therapeutic outcomes for rheumatoid arthritis (RA) Iraqi patients. An observational cross-sectional study involving 95 RA patients with established RA patients based on their methotrexate treatment responsiveness. Genetic sequencing of the TYMS gene was performed for all patients according to the instruction manuals of the sequencing company (Macrogen Inc. Geumchen, South Korea). Four polymorphisms were identified by sequencing 95 randomly selected patients in the noncoding region of TYMS

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Publication Date
Sat Sep 15 2018
Journal Name
Journal Of Baghdad College Of Dentistry
Evaluation of Hematocrit Level, Red Blood Cells and White Blood Cells Counts in Blood from Patients with Different Severities of Periodontal Diseases
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Background: Anemia of chronic disease (ACD) occurs in the presence of chronic infection, inflammatory conditions or neoplastic conditions despite of adequate iron and vitamins storage. Gingivitis is the inflammation of the gingiva, periodontitis is the inflammation in the periodontium that extend deeper with loss of connective tissue attachment and supporting bone. The main pathogenesis of periodontal diseases and ACD is immune activation. Aims of study: Determine and compare the clinical periodontal parameters (plaque index (PLI), gingival index (GI), bleeding on probing (BOP), probing pocket depth (PPD) and clinical attachment level (CAL)). Evaluate the hematocrit (Hct) level, red blood cells (RBCs) count and white blood cells (WBCs) c

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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
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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