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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
Mon Mar 15 2021
Journal Name
Al-academy
Anthropology and Representations of Magic in Arab Theatrical Text Harut and Marut's Play as a Model: وصال خلفة كاظم البكري
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The research (Anthropology and Representations of magic in Arab Theatrical Text, Harut and Marut's play as a Model) is concerned with studying magic and the forms of its presence in the theatrical text in different human cultures where it belongs. The research consists of four chapters.
The first chapter includes the research problem that revolves around the following questions: (what is the mechanism of employing magic anthropology and its representations in the Arab theatrical text Harut and Marut's play as a model?), and the research importance which is attributed to the necessity of studying (magic) in the Arab theatrical text as it is considered the inauguration of one of the social phenomena that many researchers in the field o

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Publication Date
Mon Jun 01 2020
Journal Name
Iop Conference Series: Materials Science And Engineering
Flow Production Rate of Hard Photons Probes of Quark–Anti Quark Annihilation Processes at Plasma Phase
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The flow emission rate of hard photons from lowest order the QCD processes for quark-anti quark annihilation processes in plasma media at high temperatures (175, 200, 225, 250 and 275 MeV) have been study. In these framework photons, the flow photons emission is calculate according to quark-antiquark annihilation using the quantum chromodynamic theory and solves the ultrarelativistic equation with MATLAP program. Due to the results, we show increases flow photons rate with increases strength coupling and increases with increases temperature of media, it indicate that logarithmically divergent thermal effect on photons product. The critical temperature (Tc=155 to 195 MeV) effect on the quarks confined in hadronic matter phase, it is importan

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Publication Date
Mon Mar 09 2026
Journal Name
Актуальные проблемы обучения русскому языку Xiii
ARABIC PHONO-GRAMMAR AND ITS RUSSIAN EQUIVALENTS AS A NEW APPROACH IN FL TEACHING (RUSSIAN AND ARABIC IN RUSSIAN AND ARABIC CLASSROOMS)
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Central and Eastern European Online Library - CEE journals, documents, articles, periodicals, books available online for download, Zeitschrfitendatenbank, Online Zeitschriften, Online Zeitschriftendatenbank

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Publication Date
Tue Dec 01 2020
Journal Name
Systematic Reviews In Pharmacy)srp)
Evaluation the response to infliximab therapy in patients with ulcerative colitis and crohn's disease
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Publication Date
Wed Oct 29 2025
Journal Name
Journal Of Molecular Histology
Artemisinin effects on Gastrointestinal tissues in Candida albicans-infected mice: histological and functional evaluation
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Publication Date
Sat Jun 25 2022
Journal Name
International Journal Of Drug Delivery Technology
Evaluation of the Possible Protective Effect of Fisetin against Cyclophosphamide-induced Genotoxicity in Bone Marrow and Spleen Cells of Male Rats
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Fisetin is a plant flavonoid found in strawberries and other fruits and vegetables such as apples, persimmons, and onions. It has many pharmacological effects like anti-inflammatory, antioxidant, cardioprotective, neuroprotective, and anti-carcinogenicity which are attributed to its ability to reduce oxidative stress which considers the main reason for different disease conditions. Genotoxicity refers to the genetic material destruction within the cell which can be caused by different chemicals as well as radiation. The present study evaluates the effect of orally-administered fisetin daily for seven constitutive days on genotoxicity induced by cyclophosphamide in rats’ bone marrow and spleen cells. Results showed that fisetin exh

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Publication Date
Thu Mar 31 2016
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Kinetics and Mass Transfer Study of Oleic Acid Esterification over Prepared Nanoporous HY zeolite
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A mathematical model was proposed to study the microkinetics of esterification reaction of oleic acid with ethanol over prepared HY zeolite catalyst. The catalyst was prepared from Iraqi kaolin source and its properties were characterized by different techniques. The esterification was done under different temperature (40 to 70˚C) with 6:1 for molar ratio of ethanol to oleic acid and 5 % catalyst loading.

   The microkinetics study was done over two period of time each period was examined individually to calculate the reaction rate constant and activation energy. The impact of the mass transfer resistance to the reactant was also investigated; two different studies have been accomplished to do this purpose.

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Publication Date
Wed Mar 30 2016
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Kinetics and Mass Transfer Study of Oleic Acid Esterification over Prepared Nanoporous HY zeolite
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A mathematical model was proposed to study the microkinetics of esterification reaction of oleic acid with ethanol over prepared HY zeolite catalyst. The catalyst was prepared from Iraqi kaolin source and its properties were characterized by different techniques. The esterification was done under different temperature (40 to 70˚C) with 6:1 for molar ratio of ethanol to oleic acid and 5 % catalyst loading.    The microkinetics study was done over two period of time each period was examined individually to calculate the reaction rate constant and activation energy. The impact of the mass transfer resistance to the reactant was also investigated; two different studies have been accomplished to do this purpose.    The e

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Publication Date
Mon Mar 15 2021
Journal Name
Egyptian Journal Of Chemistry
Antimicrobial Activity of New Synthesized Aza -Beta Lactam and Tetrazole Derivatives Bearing Imidazo[2,1-B]Benzothiazole Moiety
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Publication Date
Sun Sep 04 2016
Journal Name
Baghdad Science Journal
Synthesizing, Characterizing and Studying the Biological Activity of Some New Schiff-Bases Derivatives Containing the Monosaccharide Moiety
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A new series of ?-D-glucose as Schiff bases derivatives is synthesized and characterized with studying their bioactivity. Hydroxyl groups at C (1,2&5,6) sugar moiety are converted into acetal form through a reaction with dry acetone using phosphoric acid and anhydrous zinc chloride as catalysts producing 1,2:5,6-di-O-isopropyledine ?-D-glucofuranose(I). The five memberd ring acetal of C(5,6) is hydrolyzed with acetic acid (65%)and a reaction of the new product with sodium periodate is carried on to get an aldehyde moiety which is used to produce a new series of Schiff bases through reacting with different amino compounds such as 4-amino antipyrene . The suggested chemical structures of the prepared compounds are confirmed by using UV., FT

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