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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 Mar 15 2023
Journal Name
Bionatura
Study the antioxidant of Matricaria chamomilla (Chamomile) powder: In vitro and vivo
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Oxidative stress is oxidative damage caused by free radicals and reactive oxygen species (ROS). These ROS can cause oxidative damage to cellular components, including membrane lipids, receptors, enzymes, proteins, and nucleic acids. It would eventually lead to cell apoptosis and the appearance of certain pathological conditions. This work investigates the antioxidant potentials of chamomile extract in vitro by evaluating the extract activity to scavenge 2,2-Diphenyl-1-picrylhydrazyl (DPPH), also in vivo by investigating its effects on oxidative stress-induced rats by assessing the total oxidant status (TOS) and total antioxidant capacity in the radiation exposed rats with and without the treatment with chamomile extract. The results

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Publication Date
Sun Nov 01 2020
Journal Name
Journal Of Physics: Conference Series
Synthesis, characterization and biological evaluation of thiazolyl azo ligand complexes with some metal ions.
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(E)-2-(benzo[d]thiazol-2-yliazenyl)-4-methoxyaniline was synthesized by reaction the diazonium salt of 2-aminobenzothiazole with 4-methoxyaniline. Identified of the ligand by spectral techniques (UV-Vis, FTIR,1HNMR and LC-Mass) and microelemental analysis (C.H.N.S.O) are used to produce of the azo ligand. Complexes of (Co2+, Ni2+, Cu2+ and Zn2+) were synthesized and identified using atomic absorption of flame, elemental analysis, infrared and UV-Vis spectral process as well conductivity and magnetic quantifications. Nature of compounds produced have been studied followed the mole ratio and continuous contrast methods, Beer's law followed during a concentration scope (1×10-4-3×10-4 mole/L). height molar absorptivity of compound solutions h

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Publication Date
Mon Sep 30 2013
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Synthesis, Characterization and Evaluation of Overbased Magnesium Fatty Acids Detergent for Medium Lubricating Oil
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A series of overbased magnesium fatty acids such as caprylate, caprate, laurate, myristate, palmitate, stearate and oleate) were synthesized by the reaction of the fatty acids with active – 60 magnesium oxide and carbon dioxide (CO2) gas at 60 oC in the presence of ammonia solution as catalyst, toluene / ethanol solvent mixture (9:1vol/vol) was added.
The prepared detergent additives were characterized by FTIR, 1HNMR and evaluated by blending each additive in various concentrations with medium lubricant oil fraction (60 stock) supplied by Iraqi Midland Refineries Company. The total base number (TBN, mg of KOH/g) was determined, and the results of TBN were treated by using two-way analysis of variance (ANOVA) test. It was found that

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Publication Date
Tue Mar 28 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Design, Synthesis, Characterization and Comparative Cytotoxic Evaluation of bis-(2- mercaptoacetate) gold (III) chloride
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In recent years , the interest in gold (III) species have gained more and more attention for cancer chemotherapy , this was stimulating by the possibility to develop new agents with mode of action and clinical profile different from the established platinum metalodrugs.

With this frame, recently new square planar Au(III)  complexes (Au(L)(L')n); where L=SCH2COO- ; L'=HSCH2COO- had been synthesized with S/O – donor ligands.

In this article and by the aim to replace, one of (L') ligand by anion chloride ligand (which supposedly more relevant for the biodistribution of the compound than for its pharmacodynamic effects), new complex (Au(L')

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Publication Date
Thu Jan 24 2019
Journal Name
Journal Of Education College Wasit University
Postmodernism and Technology in Don Delillo's Novel The White Noise
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This paper aims at investigating the effect of postmodernism and technology on the social life in Don Delillo's novel The White Noise. In this novel, Don Delillo portrays the chaotic life by using modern technology which has been presented by three ways. The first way is by television as being a source of information and entertainment. The second way is by the toxic event whereas the third is by Dylar's episode and its destructive consequences. He depicts that through the atmosphere of Jack's family plus its effects on the life and thoughts of the elders and society. He proves that technology is leading humanity not to safety, but to death. He further highlights that by showing the impact of technology on the life of the main charac

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Publication Date
Sat Oct 28 2023
Journal Name
Baghdad Science Journal
Synthesis and Characterization of Calcium Oxide Impregnated on Silica from Duck Egg Shells and Rice Husks as Heterogeneous Catalysts for Biodiesel Synthesis
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Biodiesel can be prepared from various types of vegetable oils or animal fats with the aid of a catalyst.
Calcium oxide (CaO) is one of the prospective heterogeneous catalysts for biodiesel synthesis. Modification
of CaO by impregnation on silica (SiO2) can improve the performance of CaO as catalyst. Egg shells and rice
husks as biomass waste can be used as raw materials for the preparation of the silica modified CaO catalyst.
The present study was directed to synthesize and characterize CaO impregnated SiO2 catalyst from biomass
waste and apply it as catalyst in biodiesel synthesis. The catalyst was synthesized by wet impregnation
method and characterized by x-ray diffraction, x-ray fluorescence, nitr

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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 Dec 01 2019
Journal Name
Saudi Medical Journal
The diagnostic power of circulating micro ribonucleic acid 34a in combination with cancer antigen 15-3 as a potential biomarker of breast cancer
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Publication Date
Mon Dec 20 2021
Journal Name
Baghdad Science Journal
Recurrent Stroke Prediction using Machine Learning Algorithms with Clinical Public Datasets: An Empirical Performance Evaluation
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Recurrent strokes can be devastating, often resulting in severe disability or death. However, nearly 90% of the causes of recurrent stroke are modifiable, which means recurrent strokes can be averted by controlling risk factors, which are mainly behavioral and metabolic in nature. Thus, it shows that from the previous works that recurrent stroke prediction model could help in minimizing the possibility of getting recurrent stroke. Previous works have shown promising results in predicting first-time stroke cases with machine learning approaches. However, there are limited works on recurrent stroke prediction using machine learning methods. Hence, this work is proposed to perform an empirical analysis and to investigate machine learning al

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Publication Date
Sun Jun 08 2025
Journal Name
Journal Of Natural Science, Biology And Medicine
The Value of White Blood Cells and Platelets Indices in Prediction of Tubal Ectopic Pregnancy Rupture
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