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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 May 16 2023
Journal Name
Political Sciences Journal
The Dens of Extremism and Terrorism in Syrian Camps (Al-Hol as a model)
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After the defeat of the military terrorist organization "ISIS" and the fall of the throne of its alleged state in the Iraqi city of Nineveh, in Syrian Baghouz, and the end of its control over the land, the Syrian camps, especially "Al-Hol" camp, emerge as an incubator for the ideology of the terrorist organization "ISIS" and a vital base for its consolidation and dissemination, which includes (68,000- 73,000) people. During the years following the military defeat of (ISIS), the camp witnesses the spread of extremist ideas widely at the hands of its residents, including the families of the organizations dead's, extremist detainees, and those who deal with it, taking advantage of the deterioration of the environmental, se

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Publication Date
Thu Apr 25 2019
Journal Name
Iraqi Journal Of Market Research And Consumer Protection
DETERMINATION OF SOME TRACE ELEMENTS IN HUMAN HAIR AS ENVIRONMENTAL POLLUTION INDICATOR.: DETERMINATION OF SOME TRACE ELEMENTS IN HUMAN HAIR AS ENVIRONMENTAL POLLUTION INDICATOR.
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Trace Elements (Cd, Pb, Cu, Zn, Ni) level were examined in hair of donors from industrial areas, cities and village, and in permanent contact with a polluted workplace environment in lattakia. Hair sample were analyzed for their contents of the trace elements by inductivity coupled plasma- mass spectrometer (ICP- MS). It was found that the contents of (Cd, Pb, Cu, Zn, Ni) in the hair were significantly higher in the industrial areas and cities, while in the village had the lower concentration of elements. Correlation coefficients between the levels of the elements in hair found in this study showed that hair is a good indicator of Environmental Pollution.

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Publication Date
Fri Dec 23 2022
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Anti-obesity effect of simvastatin and omega-3 and its combination on obese model male Wistar rats
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      Strategies to reduce obesity have become main priority for many health institution and health staff around the world, as the prevalence of obesity has risen and exacerbated in most of the world mainly because of the modern life style which tend to be more sedentary with an increase eating unhealthy fast western food. Many years ago, the lipid-lowering drug simvastatin; and omega-3 were considered as a traditional lipid-lowering drug that have been well-documented to possess anti-inflammatory, cardioprotective and triglyceride-lowering properties; and their co-administration may demonstrate a complementary effect in lowering patients' triglycerides and total cholesterol to treat atherosclerosis. Many previous studies have

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Publication Date
Wed Jan 01 2020
Journal Name
Systematic Reviews In Pharmacy
Anti-Oxidoreductive stress Effects of Iraqi Olea Europaea L. Leaves extract against low double doses of alloxan induced diabetes mellitus in rats
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Olive leaves extract is famous for its antioxidant and protective effects. In this study, the aqueous extract of Iraqi Olea europaea L. Leaves was investigated for its anti-diabetic effects against low double doses of alloxan induced Diabetes Mellitus in rats. Low double doses (75 mg\Kg body weight) of alloxan were injected intraperitoneally at day 1&29 of the experimental period in rats, whereas an aqueous extract of Iraqi Olea europaea L. Leaves was added continuously to their drinking water. Serum malondialdehyde concentration, total oxidative stress and oxidative stress index as oxidoreductive stress biomarker, activities of certain antioxidoreductive stress enzymes (glutathione peroxidase, super oxide dismutase and catalase) and concen

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Scopus
Publication Date
Wed Jan 01 2020
Journal Name
Systematic Reviews In Pharmacy
Anti-Oxidoreductive stress Effects of Iraqi Olea Europaea L. Leaves Extract against Low Double Doses of Alloxan Induced Diabetes Mellitus in Rats
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Olive leaves extract is famous for its antioxidant and protective effects. In this study, the aqueous extract of Iraqi Olea europaea L. Leaves was investigated for its anti-diabetic effects against low double doses of alloxan induced Diabetes Mellitus in rats. Low double doses (75 mgKg body weight) of alloxan were injected intraperitoneally at day 1&29 of the experimental period in rats, whereas an aqueous extract of Iraqi Olea europaea L. Leaves was added continuously to their drinking water. Serum malondialdehyde concentration, total oxidative stress and oxidative stress index as oxidoreductive stress biomarker, activities of certain anti-oxidoreductive stress enzymes (glutathione peroxidase, super oxide dismutase and catalase) and concen

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Publication Date
Thu Dec 01 2022
Journal Name
Tropical Journal Of Natural Product Research
Alterations in Biochemical Parameters and Antioxidant Enzymes in Male Mice as Biomarkers of Exposure to Pollution with Cadmium
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There is currently a significantly larger concentration of toxins in our environment than there was in the past. This is mostly attributable to the expansion of modern industry. This investigation was conducted in order to investigate various haematological and biochemical changes in order to determine the effects of Cd on the liver and kidney. Because of its long biological half-life, it is considered hazardous to human health. The effect of sub-lethal doses (40, 80 and 120 mg\Kg) of Cadmium (Cd) on male mice were evaluated for 4 weeks, and analysis was done to estimate their biochemical parameters and antioxidant enzymes. The results showed that Cd-treated mice had considerably lower packed cell volume, red blood cells, and haemoglobin. W

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Publication Date
Sun Jan 01 2023
Journal Name
Journal Of Medicinal And Chemical Sciences
An Evaluation of Activity of Prepared Zinc Nanoparticles with Extract Green Plant in Treatments of Diclofenac, Levofloxacin, and Tetracycline in Water
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Myrtle plant was washed, dried, and powdered after harvesting to produce a fine powder used in water treatment. An alcoholic extract was created from the myrtle plant using ethanol, which was then analyzed using GC-Mass, Fourier Transform Infrared spectroscopy, and ultraviolet-visible spectroscopy to identify the active components. Zinc nanoparticles were created using alcoholic extract. FT-IR, UV-Vis, SEM, EDX, and TEM were used to characterize zinc nanoparticles. Using a continuous processing procedure, zinc nanoparticles with myrtle extract and powder were employed to clean polluted water containing pesticides and antibiotic. First, 2 g of zinc nanoparticles was mixed with 20 ml of polluted water and the result was (Tetra 44%, Levo 32%),

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Publication Date
Thu Jun 27 2024
Journal Name
International Journal Of Heat And Technology
Experimental and Theoretical Study of a Novel Hydraulic Fluid Flow Control Method
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Publication Date
Fri Jul 01 2022
Journal Name
Iop Conference Series: Earth And Environmental Science
Evaluation of Soil Quality and Health Indices in Relation to Soil Physical Properties of Fedak Farm in Holly Najaf Province
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Fadak farm project was selected to conduct this study in and to evaluate the state of quality and health indices in term of soil physical properties, where this farm is located in Holly Najaf Governorate. Some physical properties (soil texture, mean weight diameter, bulk density, porosity, infiltration rate, saturated hydraulic conductivity and available water) were selected to assess the quality then health indices, Results showed that classes of moderate and poor soil health were dominated in lands of this farm for physical properties It was noted that the class good of soil health wasnot collaterally appeared in areas for the physical characteristics.

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Publication Date
Fri Nov 02 2018
Journal Name
Iraqi National Journal Of Nursing Specialties
Evaluation of Nursing Knowledge and Practices Concerning Nursing Care of Patient with Skin Traction in Orthopedic Units in Kurdistan Region
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Objective: The study aimed to evaluate knowledge and practices of nursing staff at the orthopedic units
regarding the existing care of patient with skin traction.
Methodology: The sample consists of (40) nurses, (20) of them from Emergency Teaching Hospital in Duhok
and the other (20) of them from Erbil Teaching Hospital in Erbil from 1st Dec. 2004 to the end of June 2005 in
Kurdistan Region.
Two instruments were constructed to evaluate knowledge and practices. Evaluation of knowledge was done by
using of multiple choice questions composed of (25) questions, and evaluation of practice was done by using the
observational check list which consist of four main category (pre skin traction, during skin traction, post skin

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