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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
Fri Oct 26 2018
Journal Name
Journal Of Planner And Development
Acceptable and Unacceptable Growth of Industrial Agglomeration in Urban Environment. Baghdad as Case Study
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Publication Date
Sun Jun 21 2020
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Evaluation the Incidence of Genotoxic Effects of Artificial Food Favoring Additives in Bone Marrow Cells and Spleen Cells in Mice
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Genetic material is the most important component of cells because it contains the genetic information; hence any disruption to the structure chromosome of cells could lead to very bad results. Genotoxicity use to evaluate the safety of any chemical compounds on genetic materials. Artificial food flavoring additive are chemical substances to produce specific placebo effects added to foods but impart specific flavor to it.

The present study evaluates the genotoxic effect of artificial food flavoring additive on structure of chromosomes at three different concentrations (50%, 100%and 150%) on both bone marrow cells and spleen cells in mice for fourteen successive days. It was found that artificial food flavoring addit

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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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Publication Date
Sun Jan 01 2023
Journal Name
The Egyptian Journal Of Hospital Medicine
Evaluation of Interleukin-9 Serum Level and Gene Polymorphism in A Sample of Systemic Lupus Erythematosus in Iraqi Female's Patients.
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Background Immunological gene and serum level for interleukin- 9 rs 17317275 have been established to have linked to predisposition systemic lupus erythematosus (SLE) and its severity. SLE is a severe, systemic autoimmune disease characterized by autoantibody generation, complement activation, and immune complex deposition. In the pathophysiology of SLE, cytokines have a pleiotropic function. Recently, IL-9 was discovered to mediate strong anti-inflammatory effects in numerous cells or experimental autoimmune models. Objective This study aimed to determine the role of age, IL-9 serum level and genetic polymorphism, C-reactive protein (CRP), Anti-nuclear antibody (ANA) and Anti- double-stranded DNA (anti-dsDNA) to recognize SLE pathogenesis.

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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
Wed Jan 01 2020
Journal Name
European J Ournal Of Molecular & Clinical Medicine
Synthesis, Characterization and Antibacterial Evaluation of Mixed Ligand Complexes of 2-phenyl-2-(o-tolylamino) Acetonitrile and Histidine ligand with Co, Cu, Zn divalent Metal Ion Complexes
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Anew mixed compound complexes derived from 2-phenyl-2-(o-tolylamino) Acetonitrile as primary ligand (L1) and histidine (L2) as secondary ligand have been prepared and characterized by conventional techniques, elemental microanalysis (C.H.N), Fourier transform infrared, ultra violet-visible spectra, , flame atomic absorption, molar conductivity, magnetic susceptibility measurement and 1H-NMR spectra. From IR data which appear chelating behavior of the amino acid ligand (L2) toward transition metal ions is via carboxylate oxygen, amino nitrogen and imidazol nitrogen as tridentate ligand while second ligand (L1) chelating through N-nitrile and N-aniline, according to all above technics the octahedral shapes were expected for these complexes as

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Publication Date
Fri Jun 01 2018
Journal Name
Journal Of Engineering
Evaluation of Traffic Performance of Ahmed Urabi Square in Baghdad City
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At present, smooth movement on the roads is a matter which is needed for each user. Many roads, especially in urban areas geometrically improved because of the number of vehicles increase from time to time.

In this research, Highway capacity software, HCS, 2000, will be adopted to determine the effectiveness of roundabout in terms of capacity of roundabout, delay and level of service of roundabout.

The results of the analysis indicated that the Ahmed Urabi roundabout operates under level of service F with an average control delay of 300 seconds per vehicle during the peak hours.

The through movements of Alkarrada- Aljadiriya direction (Major Direction) represent the heaviest traff

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Publication Date
Tue Dec 30 2008
Journal Name
Al-kindy College Medical Journal
Evaluation of the Potential Role of Serum Selenium in Diabetic Patients
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Background: The altered status of some essential trace elements observed in diabetes could have deleterious influences on the health of the diabetics. Objectives: To estimate and study the potential role of serum Selenium in type 1, type 2 diabetics and healthy subjects; and its relation with lipid profile and glycemic index. Methods: A case control designed study was carried out at the National Diabetes Center (NDC) / Al-Mustansiria University; on a total of 94 participants formed of 32 type 1 diabetics, 32 type 2 diabetics and 30 healthy control participants. Data collected about age, sex and BMI; also, blood samples examined for FPG, HbA1C, serum total cholesterol, HDL cholesterol, non-HDL cholesterol, serum triglyceride and sera were

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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
Mon Jan 01 2024
Journal Name
Baghdad Science Journal
Study of the Anticancer and Antimicrobial Biological Activity of a New Series of Thiohydantoin Derivatives
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        Recently, some prostate cancer patients have acquired resistance to the second -generation drugs (anzalutamide and apalutamide) prescribed for the treatment of this disease due to the emergence of the F876L mutation, which represents a challenge to modern medicine. In this study, a new series of 2-thiohydantoin derivatives were prepared through the reaction of different derivatives of maleimide (1c-4c) with isothiocyanate derivatives. The prepared compounds were diagnosed using FT-IR,1H-NMR ,13C-NMR, Mass spectra. The prepared series compounds has been studied against prostate cancer cells. The MTT assay was used to determine the activity of the prepared compounds against prostate cancer cells. The da

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