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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
Mon Oct 01 2018
Journal Name
World Journal Of Pharmacy And Pharmaceutical Sciences
THE ANTIBACTERIAL EFFECT OF FLAXSEED EXTRACT ON SELECTIVE ORAL PATHOGENS - COMPARATIVE IN VITRO STUDY
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Flaxseed from the flax plant (Linum usitatissimum), which has been cultivated for domestic use since prehistoric times. This study aims to investigate presence of antibacterial effect of flaxseed extract against selected oral pathogen in-vitro.

Publication Date
Sat Mar 01 2008
Journal Name
Al-khwarizmi Engineering Journal
Evaluation of Hydrated Lime Filler in Asphalt Mixtures
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Mineral filler is one of important  materials and affecting on properties and quality of asphalt mixtures .There are different types of mineral filler depended on cost and quality , the matter encourages us to achieve this study to evaluate hydrated lime filler effects on properties of asphalt mixes related with strength and durability. Conventional asphaltic concrete mixtures with Portland cement and soft sandstone fillers and mixtures modified with hydrated lime were evaluated for their fundamental engineering properties as defined by Marshall properties , index of retained strength , indirect tensile strength , permanent deformation characteristics , and fatigue resistance .A typical dense graded mixture employed in construction

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Publication Date
Sun Jul 09 2023
Journal Name
Journal Of Engineering
Evaluation of Pedestrians Walking Speeds in Baghdad City
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This research examines the factors which influence pedestrian's walking speed in Baghdad. the variations in walking speed of pedestrians are related to pedestrian characteristics such as gender, age group, and clothing traditions. Using the established methodology, the counts of pedestrians were performed using manual and video counting. The case study was performed in two streets located in a highly crowded commercial zone at the city center of Baghdad: Al-Karada Dakhel and Al- Sina’a Street. Data were subjected to statistical analysis using IBM SPSS Statistics 19 software. It has been found that Iraqi pedestrians walk slower than other pedestrians in the developed countries or in the region with minimum walking speed of 29.85 m/min.

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Publication Date
Mon Aug 01 2022
Journal Name
Journal Of Engineering
Evaluation of Elaj Irrigation Project in Babil Governorate
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Climate change causes water shortage (water scarcity) in addition to the dams built by neighboring countries, which caused a lack of Iraq's water share. Therefore, evaluating the irrigation system requires considering its suitability, adequacy, and efficiency. Irrigation is considered adequate when it maintains water availability within the root zone, and if the amount to be added is determined, irrigation efficiency becomes possible by avoiding water loss. Babil Governorate is considered one of the agricultural governorates in the country that depends on its irrigation from Shatt Al-Hilla. The study area is the Elaj project. Three fields were selected for the project (B1, B2, and B3). These fields are lo

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Publication Date
Sat Sep 01 2012
Journal Name
2012 8th International Conference On Wireless Communications, Networking And Mobile Computing
Performance Evaluation of Location Management in GSM Networks
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Publication Date
Thu Sep 01 2016
Journal Name
Journal Of Engineering
Evaluation of Maintenance Management in Iraqi Governmental Buildings
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Impact of buildings in Iraq and other countries on the environment is obvious; this problem began to take scientific and humanitarian dimensions in order to reduce and eliminate this problem. This impact can be seen through the energy, water and raw materials consumed for the establishment, operation and maintenance of these buildings, as well as the emissions of hazardous gases and generations of solid wastes.

This work was conducted to assess the current maintenance managerial practice for the governmental buildings to stand on the main obstacle and extrapolation of measures by means of interviews with experts to determine the effective factors and closed questionnaire to state the features and the need for new

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Publication Date
Tue Mar 29 2022
Journal Name
Journal Of The Mechanical Behavior Of Materials
Prediction of bearing capacity of driven piles for Basrah governatore using SPT and MATLAB
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Based on the results of standard penetration tests (SPTs) conducted in Al-Basrah governorate, this research aims to present thematic maps and equations for estimating the bearing capacity of driven piles having several lengths. The work includes drilling 135 boreholes to a depth of 10 m below the existing ground level and three standard penetration tests (SPT) at depths of 1.5, 6, and 9.5 m were conducted in each borehole. MATLAB software and corrected SPT values were used to determine the bearing capacity of driven piles in Al-Basrah. Several-order interpolation polynomials are suggested to estimate the bearing capacity of driven piles, but the first-order polynomial is considered the most straightforward. Furthermore, the root means squar

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Publication Date
Thu Dec 01 2022
Journal Name
Environmental Nanotechnology Monitoring & Management
Green approach for the synthesis of graphene glass hybrid as a reactive barrier for remediation of groundwater contaminated with lead and tetracycline
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Publication Date
Tue Dec 04 2018
Journal Name
Iraqi Journal Of Market Research And Consumer Protection
EVALUATION OF IMPACT OF MARKETING POLICY IN Al-FURAT GENERAL COMPANY FOR CHEMICAL INDUSTRIES AND PESTICIDES: EVALUATION OF IMPACT OF MARKETING POLICY IN Al-FURAT GENERAL COMPANY FOR CHEMICAL INDUSTRIES AND PESTICIDES
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Marketing is one of the most important pillars on which most industrial and commercial sectors depend on evaluating their performance, improving their financial position, development and economic growth. The presence of effective marketing activities in any industrial or commercial organization (which works to meet the requirements of customers in order to ensure the integration of trading and handling rings with consumers and to ensure the growth of the marketing process regularly and not to retreat) effectively contributes to maintaining the company's position between its competitors and its customers. It is necessary to have these marketing activities in order to meet the requirements of the organization on the one hand and to

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Publication Date
Sun Dec 04 2016
Journal Name
Baghdad Science Journal
Biochemical Study on Anti Thyroid Peroxidase in Type 2 Diabetic patients with thyroid disorders
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Type 2 diabetes mellitus (T2DM) is the most frequent endocrinal disease commonly associated with thyroid disorders .The study is conducted at the Specialized Center for Endocrinology and Diabetes in Baghdad ,during December 2014 up to October 2015.This study was done to investigate the prevalence of anti- thyroid peroxidase (Anti-TPO) antibody in patients suffered from type 2 diabetes with thyroid disorders .The study groups included a total number of 80 subjects consisting of 60 type 2 diabetic patients divided into 20 hyperthyroidism subjects (group 1) ,20 hypothyroidism subjects (group 2), 20 euthyroidism subjects (group 3) and 20 healthy controls (group 4) . The fasting blood samples were analyzed for (T3,T4,TSH) by using Vitek Immuno d

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