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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 Dec 01 2013
Journal Name
Political Sciences Journal
Scientific Activities The branch of political thought
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النشاطات العلمية لفرع الفكر السياسي

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Publication Date
Fri Dec 30 2022
Journal Name
Iraqi Journal Of Science
Using Remote Sensing Coupled with Analytic Hierarchy Process Approach for Evaluating Water Harvesting in Baglia Site
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    This research involves the application of spectral indices and GIS techniques coupled with the Analytic Hierarchy Process, to assess  Baglia site, eastern Missan, as a water harvesting potential site. The AHP and pairwise comparison have been used through select four criteria including TWI, TRI, MNDWI, and NDSI, which were deemed as impact factors for this study. All these criteria have been weighted according to their significance in the water harvesting system. The findings of the AHP analysis method explained that the WH potential zones in Baglia site were divided into three zones, namely, high,  medium, and low suitability. The findings demonstrate that  Bglia site, where the highly appropriate zone is located in the deep v

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Publication Date
Sun Oct 21 2018
Journal Name
Al–bahith Al–a'alami
Ways to face rumors in the social networking site Facebook: Research thesis from the PhD thesis
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The research deals with the subject of «ways to face rumors in the site of social networking Facebook», a research based on a doctoral thesis, as the research dealt with rumors in the most dangerous type of new media, which sites of social communication with the global community as spreading rumors of all kinds and afflicts everyone who has eyes on him Of the audience of these sites, and aims to identify the rumors on Facebook because it is one of the most popular sites in the world and the strategy of combating the rumors published by Facebook users in their personal pages and groups that organize them, as well as identify methods and methods that can be During which the face of the rumors in the said site and eliminate them t

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Publication Date
Tue Apr 09 2013
Journal Name
International Journal Of Biological & Pharmaceutical Research
Antibiofilm, antibacterial and antioxidant activities of water extract of Calendula officinalis flowers
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ABSTRACT The antibacterial and antbiofilm activities of water extract of Calendula officinalis flowers against some of enteropathogenic bacteria was studied, also phytochemical screening and determination of antioxidant activity of the extract has been investigated. The results showed that the water extract of C. officinalis exhibited a good antibacterial activity against all pathogenic bacterial isolates (Salmonella, Shigella dysenteriae, Shigella flexneri, Shigella sonnei and E. coli) especially at concentration 100 µg/ml in contrast with the control cefotan antibiotic. S. sonnei was more sensitive to extract than other bacteria with highest inhibition zone (23 mm). The preliminary phytochemical tests results indicated the presence

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Publication Date
Wed Jan 01 2020
Journal Name
International Journal Of Pharmaceutical Research
Spectrophotometric Evaluation of Paracetamol in Bulk and Pharmaceutical Preparations
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Publication Date
Mon Dec 30 2024
Journal Name
Cumhuriyet Üniversitesi Fen-edebiyat Fakültesi Sosyal Bilimler Dergisi
French Language in Iraq: Study of the Relationship between University Education and Social Activities (The Case of the University of Baghdad)
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Cumhuriyet Üniversitesi Fen-Edebiyat Fakültesi Sosyal Bilimler Dergisi | Volume: 48 Issue: 2

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Publication Date
Sun Dec 01 2013
Journal Name
Political Sciences Journal
Scientific Activities political systems
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نشاطات فرع النظم السياسية

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Publication Date
Fri Jun 28 2024
Journal Name
Al-rafidain Journal Of Medical Sciences ( Issn 2789-3219 )
Synthesis, Characterization, Molecular Docking, ADMET Study, and Antimicrobial Evaluation of New Mannich Bases of Isatin–Thiazole Imine Bases
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Background: The isatin molecule is present in many natural substances, including plants and animals, and is used to prepare compounds with various biological activities. Objectives: To synthesize a new series of isatin derivatives with the expectation that they will have antimicrobial activity. Methods: Thiazole Schiff bases were synthesized from various Mannich bases of isatin to evaluate their antimicrobial properties. Initially, Mannich bases (2a–e) were synthesized by reacting isatin with formaldehyde and different secondary amines. Subsequently, they were treated with 2-aminothiazole to yield the final compounds (3a–e). Spectroscopic characterization was done via FT-IR and 1H-NMR. The antimicrobial screening was conducted o

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Publication Date
Tue Jan 01 2019
Journal Name
Baghdad Science Journal
Synthesis of new five-membered hetrocyclic compounds from 2-furfuryl mercaptan derivative and evaluation of their biological activity
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A theoretical and protection study was conducted of the corrosion behavior of carbon steel surface with different concentrations of the derivative (Quinolin-2-one), namly (1-Amino-4,7-dimethyl-6-nitro-1H-quinolin-2-one (ADNQ2O)). Theoretically, Density Functional Theory (DFT) of B3LYP/ 6-311++G (2d, 2p) level was used to calculate the optimized geometry, physical properties and chemical inhibition parameters, with the local reactivity to predict both the reactive centers and to locate the possible sites of nucleophilic and electrophilic attacks, in vacuum, and in two solvents (DMSO and H2O), all at the equilibrium geometry. Experimentally, the inhibition efficiencies (%IE) in the saline solution (of 3.5%) NaCl were studied using potentiomet

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Publication Date
Wed Apr 25 2018
Journal Name
Oriental Journal Of Chemistry
Diagnosis, Structure, and In vitro Antimicrobial and Antifungal Evaluation of some Amino benzoic acids, derived Ligand Schiff base and their Mixed Complexes with Cu(II), Hg(II), Mn(II), Ni(II) and Co(II)
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