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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
Thu May 14 2009
Journal Name
Journal Of Kerbala University
Synthesis and Characterization of Novel Macrocyclic ligand and its complexes with (Co(II) ,Ni(II) ,Cu(II) ,Zn(II) , and Cd(II) ) ions.
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A new Macrocyclic Schiff base ligand Bis[4-hydroxy(1,2-ethylene-dioxidebenzylidene) pheylenediamine] [H2L] and its complexes with (Co(II) , Ni(II) , Cu(II) , Zn(II) and Cd(II)) are reported . The ligand was prepared in two steps,in the first step a solution of (o-phenylene diamine) in methanol react under reflux with (2,4-dihydroxybenzylaldeyed) to give an (intermediatecompound) [Bis-1,2 (2,4-dihydroxybenzylediene)pheylinediamine] which react in the second step with (1,2- dichloro ethane) giving the mentioned ligand.Then the complexes were synthesis of adding of corresponding metal salts to the solution of the ligand in methanol under reflux with 1:1 metal to ligand ratio. On the basis of, molar conductance, I.R., UV-Vis, chloride content a

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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
Thu Jan 01 2015
Journal Name
Journal Of Plant Interactions
Photosynthetic and biochemical characterization of in vitro-derived African violet (<i>Saintpaulia ionantha</i>H. Wendl) plants to ex vitro conditions
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Publication Date
Mon Dec 30 2024
Journal Name
Iraqi Journal Of Science
Bio Synthesis, Characterization, and Evaluation of the Anticancer Activity of Gold and Silver Nanoparticles and Their Polyacetal Nanocomposite
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This study synthesized polyacetal from the reaction of polyvinyl alcohol with para-nitrobenzaldehyde. Polyacetal/polyvinylpyrrolidone polymer blends were prepared using solution casting. Gold nanoparticles (AuNPs) and silver nanoparticles (AgNPs) were biosynthesized using onion peel extract as the reducing agent. Nanocomposites were fabricated by blending polyacetal/PVP with AuNPs and AgNPs at different ratios. XRD and FESEM characterized the AuNPs and AgNPs. FTIR, FESEM, TGA, and DSC characterized the polyacetal, polymer blends, and nanocomposites. DSC and TGA confirmed the improved thermal stability of the polymer blends and nanocomposites. Nanocomposites demonstrated higher efficacy in inhibiting lung cancer cell lines compared t

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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
Thu Jan 23 2020
Journal Name
Oncology Letters
Overexpression of HURP mRNA in head and neck carcinoma and association with in�vitro response to vinorelbine
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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
Sun Mar 05 2017
Journal Name
Baghdad Science Journal
Study the Effects of Olive Leaves Extracts in the activity of the enzyme GOT and their Biological Activities
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The olive tree, has been used it is important plant for the time being some of their parts on a large scale in the treatment of gastrointestinal disorders and stimulate circulation . Moreover, it is used as antibacterial material and also to address some of the respiratory system, diabetes, food preservation osteoporosis. This study involved the collection of olive leaves from different areas in Baghdad / Iraq. These leaves have been harvested, wash it, then dried and crushed, where the study aimed to identify the active ingredients and chemical elements in the olive leaf as well as its effect on the action of GOT enzyme .The study showed that the aqueous extracts (cold and hot) of the olive leaves powder are acidic in nature pH values

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Publication Date
Mon May 11 2020
Journal Name
Baghdad Science Journal
Estimating Lipoxygenase and Gamma-glutamyl Transferase Activities in Sera of Colon Cancer Patients with Partial Purification of Lipoxygenase
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            Colon cancer is an abnormal growth of cells that occurs in the large intestine. Sometimes growth remains restricted for a relatively long time before it becomes a malignant tumor and then spreads through the intestinal wall to the lymph nodes and other parts of the body. The study aims to estimate the effectiveness and partial purification of lipoxygenase (LOX) enzyme and measure gamma-glutamyle transferase (GGT) activity in serum patients of colon cancer in Baghdad. The study included (80) case male patients with colon cancer with (50) samples of apparently healthy males (control) as comparison group. The result displayed a noteworthy increase in lipoxygenase effectivene

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Publication Date
Thu Dec 28 2017
Journal Name
Ibn Al-haitham Journal For Pure And Applied Science
Synthesis, Characterization and Biological Evaluation of New Dithiocarbamate Ligand and Its Complexes with some Metal Ions
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New bidentate dithiocarbamate ligand (NaL) namely [Sodium-2-(((3-methyl -4- “(2,2,2-tri fluoro ethoxy) pyridin-2”-yl) methyl) sulfinyl)-1H-benzoimidazole -1-carbodithioate] was prepared. This free ligand was synthesized from the reaction of a (RS)-2-([3-methyl -4-(2,2,2-tri fluoroethoxy) pyridin-2-yl] methyl sulfinyl)-1H benzoimidazole, CS2 and NaOH in methanol as solvent. From reaction of dithiocarbamate salt (NaL) with metal ions (M); Co(II), Ni(II), Cu(II), Zn(II), Cd(II) and Pd(II)”, have obtained the DTC complexes at general molecular formula [M(L)2(H2O)2] and [Pd(L)2]. To characterize the ligand and its complexes, used different analyses methods such FTIR, UV-Vis, elemental microanalysis, atomic absoreption, magnetic susceptibil

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