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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
Thu Mar 02 2023
Journal Name
East European Journal Of Physics
Evaluation of the Influence of Body Mass Index and Signal-to-Noise Ratio on the PET/CT Image Quality in Iraqi Patients with Liver Cancer
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Image quality has been estimated and predicted using the signal to noise ratio (SNR). The purpose of this study is to investigate the relationships between body mass index (BMI) and SNR measurements in PET imaging using patient studies with liver cancer. Three groups of 59 patients (24 males and 35 females) were divided according to BMI. After intravenous injection of 0.1 mCi of 18F-FDG per kilogram of body weight, PET emission scans were acquired for (1, 1.5, and 3) min/bed position according to the weight of patient. Because liver is an organ of homogenous metabolism, five region of interest (ROI) were made at the same location, five successive slices of the PET/CT scans to determine the mean uptake (signal) values and its standard deviat

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Publication Date
Sat Dec 31 2022
Journal Name
Al-kindy College Medical Journal
Assessment of Serum Level of Protein Carbonyl as a Marker of Protein Oxidation in Patients with Type 2 Diabetes Mellitus
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Background: Diabetes mellitus is a chronic disease with an increasing prevalence worldwide and characterized by an increase in oxidative stress and inflammation. The most important factor that is responsible for oxidative stress and production of reactive oxygen species (ROS) is hyperglycemia. The major targets of ROS are proteins. The most common and widely used biomarker of severe oxidative protein damage is protein carbonyl content.

The study was designed to assess the serum level of protein carbonyl as a marker of protein oxidation in patients with type 2 diabetes mellitus and to evaluate the effect of age, body weight, waist circumference, diabetic control and disease duration on the level

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Publication Date
Sun Jun 01 2014
Journal Name
Baghdad Science Journal
Evaluation of the Organic-Pollution Based on the Determination of some Polycyclic Aromatic Hydrocarbons(PAHs) in Tigris River Water in 2012 at Baghdad City , Iraq
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This study aims to predict the organic pollution produced from the presence of some polycyclic aromatic hydrocarbons (PAHs) and determination it's concentrations (µg/L , ppb) in Tigris river water by a collection twenty-seven water samples from a selected three stations with nine sampling sites and three depths of water (5 cm , 2 m and 4 m) each site for 4.6 km distance of a geographic studied area which is located between the ( Al-Senak and AL-Sarrafiah bridges ) at Baghdad city – Iraq on May, 2012. The geographic location was determined with a Global Positioning System (GPS) and Geographic Information System (GIS) software program. The concentrations of fourteen components (PAHs) were performed using the reverse phase

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Publication Date
Fri Mar 01 2024
Journal Name
International Immunopharmacology
Evaluation of interleukins (IL-1α, IL-1Ra, IL-12, IL-17A, IL-31, and IL-33) and chemokines (CXCL10 and CXCL16) in the serum of male patients with ankylosing spondylitis
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Publication Date
Sun Apr 24 2022
Journal Name
Egyptian Journal Of Chemistry
A novel Tubular Electrochemical Reactor with a Spiral Design of Anode for Treatment of Petroleum Refinery Wastewater
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Publication Date
Wed Dec 30 2015
Journal Name
Al-kindy College Medical Journal
Association between glycaemic control and serum lipid profile in type 2 diabetic patients: Glycatedhaemoglobin as a dual biomarker
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Background: Patients with type 2 diabetes have an increased prevalence of lipid abnormalities, contributing to their high risk of cardiovascular diseases (CVD).Glycated hemoglobin (HbA1c) is a routinely used marker for long-term glycemic control. In accordance with its function as an indicator for the mean blood glucose level, HbA1c predicts the risk for the development of diabetic complications in diabetic patients[2].Apart from classical risk factors like dyslipidemia, HbA1c has now been regarded as an independent risk factor for (CVD) in subjects with or without diabetes.Objective The aim of this study was to find out association between glycaemic control (HbA1c as a marker) and serum lipid profile in type 2 diabetic patients.Methods

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Publication Date
Sat Jun 01 2013
Journal Name
Journal Of The College Of Basic Education
Beta-2-Microglobulin as a Biomarker in Iraqi Female Patients with Autoimmune Thyroid and Renal Autoimmune Thyroid Diseases
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The present study was performed on 80 female subjects between (30-60) years, who attended the Specialized Center for Endocrinology and Diabetes during the period from April to July; 2011. The subjects were divided into 3 groups : controls , non diabetic autoimmune thyroid patients , and non diabetic autoimmune thyroid patient with renal diseases as complication The results showed a significant increase in serum T 3 T4 levels in hyperthyroidism patients, and significant decrease in serum T3,T4 levels in hypothyroidism patients ,while a significant difference in serum TSH levels in hyperthyroidism and hypothyroidism patients when compared to control group The results show also a significant increase in serum antibodies to thyroid peroxidas

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Publication Date
Sat Sep 23 2023
Journal Name
Journal Of Cardiovascular And Thoracic Research
Plasminogen activator urokinase receptor as a diagnostic and prognostic biomarker in type 2 diabetic patients with cardiovascular disease
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Introduction: Cardiovascular diseases are the main cause of death among type 2 diabetic patients. Higher levels of plasminogen activator urokinase receptor have been found to predict morbidity and mortality across acute and chronic diseases in the common populace. This study aims to explore the role of serum plasminogen activator urokinase receptor levels as a cardiometabolic risk factor among type 2 diabetic Iraqi patients. Methods: Seventy type 2 diabetic patients (40 male and 30 female) (mean age: 46.20±7.56 years) participated in this study; 35 patients were with cardiovascular disease and 35 were without cardiovascular disease; their ages range was 40-55 years. In addition, 30 individuals who apparently healthy were selected a

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Publication Date
Sun Dec 15 2024
Journal Name
Arid International Journal For Science And Technology
Effect of Fertilization NPK-Nano and Humic Acid on Some Vegetative Growth Characteristics and Mineral Content of Apple Seedlings (Malus Domestica) Cv. Ibrahimi.
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The research was carried out in lathhouse on one-year-old apple seedlings of the Ibrahimi variety in the Karma-Fallujah region for the 2021 growing season to study the effect of methods of adding nano-fertilizer and humic acid on seedling growth. A two-factor experiment was designed according to a randomized complete block design, with three replicates and two seedlings per experimental unit, so the number of seedlings was 54. The first factor includes NPK nanofertilizer at three levels (0- and 2-ml L-1 foliar spray and 5 ml L-1 soil application). The second factor is humic acid at three levels (0 and 5 g of seedlings - 1 foliar spray and 10 g of seedlings - 1 soil application). The results of the study show that the NPK nano-fertil

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Publication Date
Mon Mar 08 2021
Journal Name
Baghdad Science Journal
Totas serum sialic acid among enteric fever patients
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In this study serum total sailie acid concentration were tested as a scrological marker of discases activity to cvalute the result of the test in the diagonosis oe enteric fever(TSA) was measured in the serum od (50) patines with typhi fever(50)pa-tients

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