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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 Aug 13 2017
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
In vivo study of compounds 3-(acetyl Salicyloyl)-5,6 –Oisopropylidene-L-ascorbic acid ,2,3- (acetyl Salicyloyl)-5,6 –O-isopropylidene-L-ascorbic acid and 2,3,5,6Tetra(acetyl Salicyloyl)-L-ascorbic acid
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     In vivo study was made for the coumpounds 3-(ocetyl Salicyloyl)-5,6-O-isoprpy lideneL-ascorbicocid,2,3-(acetyl Salicyloyl )-5,6-o- isopropylidene-L-ascorbic acid and 2,3,5,6(acetyl Salicyloyl )-L- ascorbic acid .And a measurement was mod for the concentration of the liberated aspirin in blood samples a fter (2,3,4,6,8,10) hours of the initial dose for the animal .The results showed that the highest concentration of aspirin was after four hours of giving the dose to the animal which is in accordance with pharmacokinetics studies

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Publication Date
Mon Jun 01 2015
Journal Name
Journal Of The College Of Languages (jcl)
Emotions conflict In Balzac’s novel The Father Goriot And Stendhal’s The Red and The Black
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Au XIXe siècle, avec l’excès de la passion, le roman français commence à avoir de nouvelles figures. Il tend à être un reflet de la pensée et de la passion. Stendhal et Balzac révèlent ainsi le conflit de l’âme et donnent à leur héros l’impression que tout est permis.

                Ces protagonistes doivent, d’une part, subir des fluctuations psychologiques, et d’autre part, ces héros doivent être capables de faire face aux rancunes et aux conflits destructeurs. Les personnages stendhaliens et balzaciens finissent par croire que leur combat ne portera pas ses fruits, parce que toute passion déséquilibrée mènera, soit à la fol

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Publication Date
Sat Dec 02 2023
Journal Name
Journal Of Engineering
Evaluation of the Stability and Flow of Asphalt Concrete Produced with Waste Brick Tile Powder as a Filler
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The utilization of recycled brick tile powder as a replacement for conventional filler in the asphalt concrete mix has been studied in this research. This research evaluates the effectiveness of recycled brick tile powder and determines its optimum replacement level. Using recycled brick tile powder is significant from an environmental standpoint as it is a waste product from construction activities. Sixteen asphalt concrete samples were produced, and eight were soaked for a day. Samples contained 5% Bitumen, 2% to 5% brick tile powder, and conventional stone dust filler. The properties of samples were evaluated using the Marshall test. It was observed that the resistance to stiffness and deformation of asphalt concrete

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Publication Date
Fri Jan 01 2021
Journal Name
Biochemical Cellular Archive
detection of anti-helicobacter pylori cag a antibody in sera of patients with eye diseases
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The study conducted to investigate the association between Helicobacter pylori infection and eye diseases (Glaucoma, Cataract, CSR and Uveitis). One hundred and four patients with multiple eye disorders (10-80) years were observed from 10/9/2020 to 18/11/2020 and compared to thirty-one healthy people (19 female and 12 male). Each participant was tested for H. pylori CagAAbs and TNF-α using an enzyme-linked immunosorbent assay (ELISA). The results have shown that there was a non-significant difference (p≥0.05) in the concentration of CagAantibodies in sera of patients with eye diseases except in the case of CSR (central serous chorioretinopathy), which was a significant difference (P≤0.05) compared to the control group. Also, the result

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Publication Date
Fri Aug 28 2020
Journal Name
Iraqi Journal Of Science
An application of Barnacle Mating Optimizer in Infectious Disease Prediction: A Dengue Outbreak Cases
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Meta-heuristic algorithms have been significantly applied in addressing various real-world prediction problem, including in disease prediction. Having a reliable disease prediction model benefits many parties in providing proper preparation for prevention purposes. Hence, the number of cases can be reduced. In this study, a relatively new meta-heuristic algorithm namely Barnacle Mating Optimizer (BMO) is proposed for short term dengue outbreak prediction. The BMO prediction model is realized over real dengue cases data recorded in weekly frequency from Malaysia. In addition, meteorological data sets were also been employed as input. For evaluation purposes, error analysis relative to Mean Absolute Percentage Error (MAPE), Mean Square Err

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Publication Date
Sun Apr 30 2023
Journal Name
Iraqi Journal Of Science
Prediction of Daily Maximum Air Temperature for Transitional Seasons by Statistical Methods in Baghdad
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     Predicting the maximum temperature is of great importance because it is related to various aspects of life, starting from people’s lives and their comfort, passing through the medical, industrial, agricultural and commercial fields, as well as concerning global warming and what can result from it. Thus, the historical observations of maximum and minimum air temperature, wind speed and relative humidity were analyzed in this work. In Baghdad, the climatic variables were recorded on clear sky days dawn at 0300 GMT for the period between (2005-2020). Using weather station's variables multiple linear regression equation, their correlation coefficients were calculated to predict the daily maximum air temperature for any day during

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Publication Date
Sun Mar 17 2019
Journal Name
Baghdad Science Journal
A Study on the Accuracy of Prediction in Recommendation System Based on Similarity Measures
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Recommender Systems are tools to understand the huge amount of data available in the internet world. Collaborative filtering (CF) is one of the most knowledge discovery methods used positively in recommendation system. Memory collaborative filtering emphasizes on using facts about present users to predict new things for the target user. Similarity measures are the core operations in collaborative filtering and the prediction accuracy is mostly dependent on similarity calculations. In this study, a combination of weighted parameters and traditional similarity measures are conducted to calculate relationship among users over Movie Lens data set rating matrix. The advantages and disadvantages of each measure are spotted. From the study, a n

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Publication Date
Sun Sep 02 2012
Journal Name
Baghdad Science Journal
Benzoic acid concentration levels recovery in Ketchup and Sauce products available in local market.
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This research is dealing with five sample of tomato ketchup products available in local market that were respectively as follows: Hello-Baghdad Iraq, Tiffany-Abu Dhabi, Melody-Dubai, Baidar-Saudi Arabia, and Altunsa-Turkey. Also it is dealing with four sample of sauce products available in local market that were respectively as follows: Hello-Baghdad, Iraq, Al-Badawi-Baghdad Iraq, Family-Baghdad, Iraq, and Hala-Amman Jordon. Analysis was performed on each sample three times and mean of the reading was taking. Samples were tested through terse and shorthand from lengthened steps. The spectrophotometric method used rely on theoretical and practical bases in extraction and diagnosis by UV spectrophotometer. This method in short notes, consiste

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Publication Date
Tue Dec 01 2020
Journal Name
Baghdad Science Journal
In Vitro Cytotoxicity Study of Pt Nanoparticles Decorated TiO2 Nanotube Array
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Titanium dioxide nanotubes were synthesized by anodizing Ti sheets in the ethylene glycol solution and were covered in Pt nanoparticles onto the surface of TiO2NTs using electrodeposition method from using five derivatives of Mannich base Pt complexes which have been used as precursor of platinum. The mean size, shape, elemental composition of the titanium dioxide nanotubes and platinum deposited on the template were evaluated by different techniques such as field emission scanning electron microscope (FE-SEM), transmission electron microscopy (TEM), X-ray diffraction pattern (XRD), and energy dispersive X-ray (EDX) technique. From all these analyses, the TiO2NTs prepared and Ptnanoparticles deposited on it were ide

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Publication Date
Mon Apr 01 2019
Journal Name
Biochemical And Cellular Archives
Influence of chemical fertilizers and foliar spraying with humic acid in growth and yield of red cabbage
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