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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
Sat Feb 05 2022
Journal Name
Applied Nanoscience
RETRACTED ARTICLE: The impact of fear on a stage structure prey–predator system with anti-predator behavior
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A prey-predator interaction model has been suggested in which the population of a predator consists of a two-stage structure. Modified Holling's disk equation is used to describe the consumption of the prey so that it involves the additional source of food for the predator. The fear function is imposed on prey. It is supposed that the prey exhibits anti-predator behavior and may kill the adult predator due to their struggle against predation. The proposed model is investigated for existence, uniqueness, and boundedness. After determining all feasible equilibrium points, the local stability analyses are performed. In addition, global stability analyses for this model using the Lyapunov method are investigated. The chance of occurrence of loc

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Publication Date
Tue Sep 02 2025
Journal Name
Journal Of Composites Science
Numerical Evaluation of Embedded I-Section Strengthening in Axially Loaded Composite Concrete-Filled Stainless Steel Tubes
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To enhance the structural performance of concrete-filled steel tube (CFST) columns, various strengthening techniques have been proposed, including the use of internal steel stiffeners, external wrapping with carbon fiber-reinforced polymer (CFRP) sheets, and embedded steel elements. However, the behavior of concrete-filled stainless-steel tube (CFSST) columns remains insufficiently explored. This study numerically investigates the axial performance of square CFSST columns internally strengthened with embedded I-section steel profiles under biaxial eccentric loading. Finite element (FE) simulations were conducted using ABAQUS v. 6.2, and the developed models were validated against experimental results from the literature. A comprehen

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Publication Date
Wed Dec 12 2018
Journal Name
Iraqi National Journal Of Nursing Specialties
Evaluation of Acute Flaccid Paralysis Surveillance System's Structure at Al-Russafa Health Directorate in Baghdad City
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Objective: evaluation of Acute Flaccid Paralysis Surveillance (AFP) System's Structure at Al-Russafa Health directorate in Baghdad City. Methodology: descriptive study using evaluation approach conducted to measure the efficiency of AFP Surveillance System structure for period from November 27th 2014 to June 30th 2015. The study adopted the non-probability multi-stage sampling approach. As nineteen health facilities under surveillance are chosen and interview is conducted with a total of 50 health worker how are involved in the AFP Surveillance System. The data are gathered from sample by using question

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Publication Date
Sun Jun 06 2021
Journal Name
Engineering, Technology & Applied Science Research
Evaluation of the Variation in Dynamic Load Factor Throughout a Highly Skewed Steel I-Girder Bridge
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The Dynamic Load Factor (DLF) is defined as the ratio between the maximum dynamic and static responses in terms of stress, strain, deflection, reaction, etc. DLF adopted by different design codes is based on parameters such as bridge span length, traffic load models, and bridge natural frequency. During the last decades, a lot of researches have been made to study the DLF of simply supported bridges due to vehicle loading. On the other hand, fewer works have been reported on continuous bridges especially with skew supports. This paper focuses on the investigation of the DLF for a highly skewed steel I-girder bridge, namely the US13 Bridge in Delaware State, USA. Field testing under various load passes of a weighed load vehicle was u

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Publication Date
Tue Oct 30 2018
Journal Name
Journal Of Engineering
Evaluation of the Project Overhead Costs in Iraqi Construction Industry using Fuzzy Analytic Hierarchy Process (FAHP)
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This research investigated the importance and priorities of the project overhead costs in Iraq via a questionnaire using the fuzzy analytic hierarchy process technique (FAHP). Using this technique is very important in the uncertain circumstances as in our country. The researcher reached to frame an equation through the results of the priorities of weights include the percentages of each of the main items of the project overhead costs. The researcher tested this equation by applying it to one of the completed projects and the results showed suitability for the application. The percentages of the (salaries, grants, and incentives) and (fieldwork requirements) in equation represent approximately two-thirds of project overhe

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Publication Date
Wed Mar 29 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Evaluation of Metformin + Sitagliptin versus Metformin + Glibenclamide on Glycemic Control in Iraqis Type 2 Diabetic Patients
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Combination therapy with a dipeptidyl peptidase–4 inhibitor and metformin or metformin+ glibenclamide results in substantial and additive glucose- lowering effects in Iraqis patients with type 2 diabetes mellitus . This study evaluated the glycemic control by using two groups of  combinations of drugs metformin + glibenclamide and metformin + sitagliptin in Baghdad teaching hospital / medical city. 68 T2DM patients and 34 normal healthy individuals as control group were enrolled in this study and categorized in to two treatment groups. The group 1 (34 patients ) received ( metformin 500 mg three times daily + glibenclamide 5 mg twice daily ) and the group 2 (34 patients) received (metformin 500 mg three times daily + sitaglip

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Publication Date
Wed Mar 29 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Evaluation of Trace Elements in Iraqi Patients with Rheumatoid Arthritis by using Atomic Absorption Spectrophotometer (AAS)
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Zinc, Copper, Selenium, Magnesium, Manganese, Chromium, Iron, Nickel, Cobalt, Vanadium and Germanium were determined by atomic absorption spectrophotometer (AAS) in blood serum of patients with rheumatoid arthritis, (30) patients (14male and 16female) with age range (37-60) years compared with normal tensive control. The analysis of results showed that the mean value of concentration (Magnesium,  Manganese and Nickel) were significantly higher in patients with rheumatoid arthritis compared to that of healthy, while the mean levels of serum (Zinc, Copper, Selenium, Chromium, Iron, Cobalt and Germanium) were significantly lower than controls. There were no significant changes in overall mean concentration of serum Vanadium in patients

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Publication Date
Sat Feb 01 2014
Journal Name
Journal Of Economics And Administrative Sciences
Evaluation the performance efficiency of the Public Manufacturing Sector in Iraq for the Period (2000-2009)
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The industrial production sector has an important role in the national economy of the advanced countries as well as the developing ones to get higher levels for their economy . We in Iraq , just like most of the develpoing countries , our economy still suffers of great shortage in this active sector in spite of the repeated statements about the desire of activating the contribution of this sector in the national economy . The industrial sector in Iraq suffers in general of many problems , especially the public industrial sector (manufacturing) . These problems have been  existed because of the unnatural conditions that Iraq has passed during the previous decades especially in the political and security sides . which reflecte

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Publication Date
Thu Jan 14 2016
Journal Name
International Journal For Sciences And Technology
Evaluation of her/2-neu gene status using FISH/CISH techniques in Iraqi breast carcinoma patients
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The present study aimed to examine the concordance between FISH/CISH techniques for assessment of amplification of her2neu gene in Iraqi breast carcinoma patients. Seventy four (74) Iraqi breast cancer patients were involved at the study from the Histopathology Department at the Central Public Health Laboratory in Bagdad, Iraq. Amplification of HER2neu was detected in (33.8%) by fluorescence in situ hybridization and (13.51%) showed high amplification by chromogenic in situ hybridization and (32.43%) showed low amplification. The results of chromogenic in situ hybridization were significantly correlated with the results of two-color fluorescence in situ hybridization with the same tumors. In addition, the study involved the correlation betw

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Publication Date
Fri Aug 26 2022
Journal Name
Journal Of Research In Medical And Dental Science
Evaluation of Some Salivary Characteristics in Relation to Dental Caries among Children with Beta-Thalassemia Major
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