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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
Tue Apr 11 2023
Journal Name
Indonesian Journal Of Chemistry
Synthesis of Co (ll), Ni (ll), Cu (ll), Pd (ll), and Pt (lV) Complexes with 14, 15, 34, 35-Tetrahydro-11 H, 31 H-4, 8-diaza-1,3 (3,4)-ditriazola-2,6 (1,4)-dibenzenacyclooctaphane-4,7-dien-15, 35-dithione, and the Thermal Stability of Polyvinyl Chloride Modified Complexes
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In the current endeavor, a new Schiff base of 14,15,34,35-tetrahydro-11H,31H-4,8-diaza-1,3(3,4)-ditriazola-2,6(1,4)-dibenzenacyclooctaphane-4,7-dien-15,35-dithione was synthesized. The new symmetrical Schiff base (Q) was employed as a ligand to produce new complexes comprising Co(II), Ni(II), Cu(II), Pd(II), and Pt(II) metal-ions at a ratio of 2:1 (Metal:ligand). There have been new ligands and their complexes validated by (FTIR), (UV-visible), 1H-NMR, 13C-NMR, CHNS, and FAA spectroscopy, Thermogravimetric analysis (TG), Molar conductivity, and Magnetic susceptibility. The photostabilization technique to enhance the polymer was also used. The ligand Q and its complexes were mixed in 0.5% w/w of polyvinyl chloride in tetrahydrofuran

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Publication Date
Tue Oct 02 2018
Journal Name
Iraqi Journal Of Physics
Study of in vitro and in vivo free radical scavenging activity for radioprotection of cerium oxide nanoparticles
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Nanoceria have shown numerous unique characteristics, such as biocompatibility and are excellent agents for biological applications. The aim of this study is to investigate cerium oxide nanoparticles for 2, 2- diphenyl-1-picryl-hydrazyl-hydrate (DPPH) free radical scavenging activity and their ability to offer protection against ionizing radiation. In vitro antioxidant activity study of nanoceria particles has shown good free radical scavenging activity for DPPH radical assayed within a concentration range of 0.01 to 0.05 g/l, at higher concentrations of nanoparticles showed reverse trend in absorbance and inhibition indicating this finite rang of concentration is suitable for scavenging free radicals, also nanoparticles were found to ha

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Publication Date
Tue Dec 01 2015
Journal Name
Journal Of Engineering
Experimental Evaluation Use of Semifluidized Bed Adsorber for the Treatment of P-chlorophenol and O-cresol in Wastewater using Activated Carbon as Adsorbent
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In the present work the performance of semifluidized bed adsorber was evaluated for removal of phenolic compound from wastewater using commercial activated carbon as adsorbent. P-chlorophenol (4-Chlorophenol) and o-cresol (2-methylphenol) was selected as a phenolic compound for that purpose. The phenols percent removal, in term of breakthrough curves were studied as affected by hydrodynamics limitations which include minimum and maximum semifluidization velocities and packed bed formation in the column by varying various parameters such as inlet liquid superficial velocity (from Uminsf to 8Uminsf m/s), and retaining grid (sometimes referred to as adsorbent loading) to initial static bed height ratio (from 3-4.5). In

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Publication Date
Mon Dec 01 2025
Journal Name
International Journal Of Humanities And Educational Research
ACADEMIC ACHIEVEMENT EVALUATION IN MODERN AND CONTEMPORARY YEMENI HISTORY STUDIES / IBN RUSHD COLLEGE OF EDUCATION -UNIVERSITY OF BAGHDAD AS A MODEL (1918-1968)
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field of modern and contemporary Yemeni history, accomplished at Ibn Rushd College of Education, University of Baghdad. It was determined according to a time frame in the years 1989, which is the date of completion of the first master’s thesis in the field of modern and contemporary Yemeni history, which deals with the subject of “Iraqi-Yemeni relations 1932- 1962”, and the year 2020, which is the year of completion of a master’s thesis on the position of Iraqi public opinion on the Egyptian military intervention in Yemen (1962-1970). The study determined the nature of these studies, whether they were in the form of master’s theses or doctoral dissertations, or research and studies published in issues of the refereed scien

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Publication Date
Sat Oct 01 2022
Journal Name
The Egyptian Journal Of Hospital Medicine
Study on Some Parameters and Anti-Rubella Igg in A Sample of Systemic Lupus Erythematosus Patients
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Publication Date
Mon Dec 30 2024
Journal Name
Iraqi Journal Of Science
Synthesis, Characterization, Thermal Studies, and Antioxidant Activities of Azo Dye[2-[(3-Hydroxyphenyl)diazinyl]-1,2-Benzothiazol-3(2H)-one-1,1-Dioxide]and Metal Ion Complexes
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The new azo dye was synthesized via the reaction of the diazonium salt form of 3-aminophenol with 2-hydroxyquinoline. This dye was then used to access a series of complexes with the chlorides of manganese, iron, zinc, cadmium, and vanadium sulfate. The prepared ligand and its complexes were characterized by FT-IR spectroscopy, UV-visible spectroscopy, mass spectrometry, thermogravimetric analysis, differential scanning calorimeter, and microelemental analysis. Conductivity, magnetic susceptibility, metal content, and chlorine content of the complexes were also measured. The ligand and cadmium complex were identified using1H NMR and 13C NMR spectroscopy. The results showed that the shape of the ligand is a trigonal planner, and the c

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Publication Date
Sun Jun 30 2019
Journal Name
Journal Of The College Of Education For Women
(Evaluation and Mobility) As Two self-Organizing Posts for University Students
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One of the important goals in the learning process is to be effective learning through the self-direction of the learner , because it has an impact on the effort of learners , it is better to be a learner responsible for learning and independent of the acquisition of knowledge ,

اذ اكدتكثيرAs many have confirmed منFrom الدراساتStudies والادبياتAnd literature انthat فشلالكثير The failure of many منFrom الطلبةStudents فيin a تنظيمgroup المعلوماتthe information ومعالجتهاAnd processed اثناءduring عمليةProcess تعلمهمLearn them لاNo يرجعReturns الىto me انخفاضdrop فيin a درجةDegree ذكائهمTheir intelligence اوor عدمNo

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Publication Date
Fri Oct 01 2021
Journal Name
Nature Communications
CD177 modulates the function and homeostasis of tumor-infiltrating regulatory T cells
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Abstract<p>Regulatory T (Treg) cells are one of the major immunosuppressive cell types in cancer and a potential target for immunotherapy, but targeting tumor-infiltrating (TI) Treg cells has been challenging. Here, using single-cell RNA sequencing of immune cells from renal clear cell carcinoma (ccRCC) patients, we identify two distinct transcriptional fates for TI Treg cells, Fate-1 and Fate-2. The Fate-1 signature is associated with a poorer prognosis in ccRCC and several other solid cancers. CD177, a cell surface protein normally expressed on neutrophil, is specifically expressed on Fate-1 TI Treg cells in several solid cancer types, but not on other TI or peripheral Treg cells. Mechanistically, blocking CD</p> ... Show More
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Publication Date
Sat Oct 01 2022
Journal Name
Al–bahith Al–a'alami
PHARAOH'S CHARACTER BETWEEN THE QUR'ANIC TEXT AND THE ARABIC NOVEL: (Naguib Mahfouz's Pharaonic Novels as a Model)
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The Character is one of the elements of Storytelling, as it is the center of the plot, making it the basis on which the talk is about. The talk is the portrayal of the character while they’re acting; the novelist presents the character by interacting with the events, and the extent of the negative and positive appearing impact on the character. It should be noted that everyone has two personalities or more, each one appearing in a different position or situation. For instance, a man can be a father, a lover, an employee, a son or anyone else .. in another position, he might be a master, and in another a looser begging for the mercy of his humiliator, and sometimes he can show weakness to the one he loves, or show strength to his enemie

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Publication Date
Sat Dec 24 2022
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Study the Effect of 12-Hydroxyoctadecanoic Acid Concentration on Preparation and Characterization of Floating Organogels using Cinnarizin as Modeling Drug
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This work targeted studying organogel as a potential floating system. Organgel has an excellent viscoelastic properties, floating system posses a depot property.  Different formulations of 12-hydroxyoctadecanoic acid (HOA) in sesame oil were gelled and selecting F1, F3 and F5 HOA organogels for various examinations: tabletop rheology, optical microscopy, and oscillatory rheology studies. Also, the floating properties studies were conducted at in vitro and in-vivo levels. Lastly, the in-vitro release study using cinnarizine (CN) was to investigate the organogel depot property. Based on the results, the selected concentrations of HOA in sesame oil organogels showed temperature transitions fr

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