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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 Dec 27 2022
Journal Name
2022 3rd Information Technology To Enhance E-learning And Other Application (it-ela)
Diabetes Prediction Using Machine Learning
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Diabetes is one of the increasing chronic diseases, affecting millions of people around the earth. Diabetes diagnosis, its prediction, proper cure, and management are compulsory. Machine learning-based prediction techniques for diabetes data analysis can help in the early detection and prediction of the disease and its consequences such as hypo/hyperglycemia. In this paper, we explored the diabetes dataset collected from the medical records of one thousand Iraqi patients. We applied three classifiers, the multilayer perceptron, the KNN and the Random Forest. We involved two experiments: the first experiment used all 12 features of the dataset. The Random Forest outperforms others with 98.8% accuracy. The second experiment used only five att

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Publication Date
Wed Sep 14 2016
Journal Name
Journal Of Baghdad College Of Dentistry
Comparison of Shear Bond Strength of Three Different Brackets Bonded on Zirconium Surfaces (In Vitro Study)
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Background: With the increased in the demands of adult orthodontics, the challenge of direct bonding to non-enamel surface (zirconium) had been increased. The present study was carried out to compare the shear bond strength of three different brackets (stainless steel, sapphire and composite) bonded to zirconium surface and study the mode of bond failure. Materials and methods: The sample was comprised of 30 models (8mm *6mm*1.5mm) of full contour zirconium veneers. They were divided into three groups according to the brackets type; all samples were treated first by sandblast with aluminum oxide particle 50 µm then coated by z-prime plus primer. A central incisor bracket of each group was bonded to the prepared zirconium surface with lig

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Publication Date
Wed Feb 11 2026
Journal Name
Journal Of Baghdad College Of Dentistry
Effect of zinc oxide nanoparticles on total salivary peroxidase activity of human saliva (In vitro study)
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Background: The potential use of zinc oxide and other metal oxide nanoparticles in biomedical are gaining interest in the scientific and medical communities, largely due to the physical and chemical properties of these nanomaterials. The present work revealed the effect of zinc oxide nanoparticles (ZnONPs) on the total salivary peroxidase enzyme activity of human saliva in comparison to de-ionized water. Materials and methods: Forty eight unstimulated saliva samples were collected from dental students/University of Baghdad 18-22 years. Then measure the total salivary peroxidase activity first without any addition to human saliva as a control, second with dilution the saliva with de-ionized water, and third with zinc oxide nanoparticles in c

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Publication Date
Sat May 02 2015
Journal Name
Advances In Life Science And Technology
Cytotoxic Effect of Aqueous Extract of Anastatica hierochuntica L. on AMN-3 Cell Line in vitro
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Anastatica hierochuntica L. is distributed throughout Arabain Peninsula, and elsewhere it is locally called "Kuffe Maryam" .All parts of the plant are used in folk medicine. This study amid to investigate the effect of aqueous extract of anastatica hierochunctica L. on the cancer cell lines AMN-3. Anti cancer activity of aqueous extract of anastatica hierochunctica L. showed anticancer activity against AMN-3 cell line for twelve concentrations (0.04, 0.09, 0.195, 0.39, 0.78, 1.56, 3.125, 6.25, 12.5, 25, 50, 100) mg/mL in comparison with negative control.

Publication Date
Tue Dec 13 2005
Journal Name
Iraqi Journal Of Laser
Stimulation of Phagocytic Activity of Human Polymorphonuclear Leukocytes in Vitro Using 10 mW He-Ne Laser.
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Stimulative effect of 10 mW He-Ne laser on the phagocytic activity of human polymorphonuclear leukocytes( PMNs) has been studied in vitro. Normal polymorphonuclear leucocytes were isolated from the human peripheral blood. A mixture of 0.25 ml of Hanks solution, 0.25 ml of serum, 0.25 ml of Candida albicans suspension and 0.25 ml of PMNs suspension was prepared. The samples of mixture of PMNs and Candida were subdivided in 1 ml ependrof tubes and irradiated to He-Ne laser for 1, 3, 5, 10 and 20 min. The diameter of the irradiated area was 0.8 cm. For calculation of Phagocytic index before and after irradiation, the samples were incubated (37°C) at 5, 15, 30, 60 min. The slides of samples were prepared and stained using Giemsa stain. The

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Publication Date
Sat Jun 06 2015
Journal Name
Advances In Life Science And Technology
Cytotoxic Effect of Aqueous Extract of Anastatica hierochuntica L. on AMN-3 Cell Line in vitro
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Anastatica hierochuntica L. is distributed throughout Arabain Peninsula, and elsewhere it is locally called "Kuffe Maryam" .All parts of the plant are used in folk medicine. This study amid to investigate the effect of aqueous extract of anastatica hierochunctica L. on the cancer cell lines AMN-3. Anti cancer activity of aqueous extract of anastatica hierochunctica L. showed anticancer activity against AMN-3 cell line for twelve concentrations (0.04, 0.09, 0.195, 0.39, 0.78, 1.56, 3.125, 6.25, 12.5, 25, 50, 100) mg/mL in comparison with negative control.

Publication Date
Sun Mar 18 2018
Journal Name
Mustansiria Dental Journal
The Effect of Pepsi Cola Beverage on Surface Roughness of Two Composite Resins (In Vitro study)
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An acidic environment causes surface changes of resin composites. Filler particlesize and filler distribution also have a direct effect on these surface changes. This invitro study evaluated the influence of Pepsi Cola drink on the surface roughness ofComposan LCM and Composan Ceram over time. Sixteen disc shaped specimens(10mm diameter, 2mm thickness) of each resin composite were fabricated, therebyforming two groups (n= 8). Surface roughness (Ra) was analyzed after 24 hrs beforeexposure to beverage. The specimens were submitted to a five minutes immersion inPepsi Cola three times daily interrupted by immersion in deionized distilled water (37C˚). Surface roughness measurements were done at 10, 30, and 60 days intervals. Datawere

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Publication Date
Sat Jan 01 2022
Journal Name
Dental Hypotheses
Comparison of Microleakage of Composite and Glass Ionomer Restorations in Primary Molars Pretreated with Silver Diamine Fluoride at Two Time Intervals: An In Vitro study
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Publication Date
Sun Sep 01 2019
Journal Name
Baghdad Science Journal
Evaluation of Physical Chemical and Biological Characteristics of Underground Wells in Badra City, Iraq
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The quality of groundwater should be improved by keeping safe water sources from contaminants in protective way by doing regular measuring and checkup before it supplied for usage. Private Wells do not receive the same services that wells supplying the public do. Well owners are responsible for protecting their drinking water. This work was carried out in Badra city, Iraq from December 2017 to May 2018, six wells water were investigated to determine the general characteristics of wells as well as studying the effect of environmental factors on the quality of water. The average of six wells were eleven parameters that is out of permissible limits were EC, Sal., Alk., TH, TDS, Na, Ca, Cl, SO4, Fe, Zn (4402-5183 /cm, 2.76-3.9 ppt

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Publication Date
Sun Dec 25 2022
Journal Name
International Journal Of Drug Delivery Technology
Effect of Zinc drug on amino acid concentration in liver of white mice, Mus musculus
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Zinc is one of the essential trace elements, it plays a key role in many biochemical and functional processes. It is less harmful than many other minerals, in the case of exposure to high doses of zinc, poisoning occurs, and this poisoning may mostly result from the accidental ingestion of household products containing zinc or nutritional supplements, this study was conducted to find out the effects of zinc on the concentration of amino acid. A total of 30 adult white mouse males were taken and divided into three groups; the first group (control) of 10 mice taken with distilled water for 30 days, the second group includes 10 mice that were dose with Zn drug concentration of 50 mg/kg/day for 30 days, the third group includes 10 mice that wer

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