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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 30 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Anti-fungal Activity of Punica Granatum I.peels Powder and Extracts from Pathogenic Samples
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Thirty five samples were collected from patients (1-30) years old, suffered from, infected skin , rushes, boils , oral thrush, anal & vaginal itches.  Candida albicans 57.3% (20 isolates) and Candida tropicalis 22.5% (8 isolates) Aspergillus  fumegatus 11.5% (4 isolates)   Aspergillus nigar 8.7%(3 isolates) , were isolated & identified from these samples.  Alcoholic & water hot extracts of the punica granatum (Pomegranate) peels as well as the dried powder were prepared.  The anti-fungal activity of the extracts was evaluated by means of the agar-well diffusion assay. The extract exhibited potent activity against yeast. The Minimum inhibitory concentra

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Publication Date
Tue Oct 29 2024
Journal Name
Current Drug Therapy
Current Nanotechnological Strategies for Delivery of Anti-Retroviral Drugs: Overview and Future Prospects
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Abstract:

Globally, over forty million people are living with Human Immunodeficiency Viral (HIV) infections. Highly Active Antiretroviral Therapy (HAART) consists of two or three Antiretroviral (ARV) drugs and has been used for more than a decade to prolong the life of AIDS-diagnosed patients. The persistent use of HAART is essential for effectively suppressing HIV replication. Frequent use of multiple medications at relatively high dosages is a major reason for patient noncompliance and an obstacle to achieving efficient pharmacological treatment. Despite strict compliance with the HAART regimen, the eradication of HIV from the host remains unattainable. Anatomical and Intracellular viral reservo

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Publication Date
Sun Aug 31 2025
Journal Name
Journal Of Science In Medicine And Life
Serum Endothelial Specific Molecule 1(EMS 1) and Uric Acid Levels in Severe Preeclampsia
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Publication Date
Thu Dec 31 2015
Journal Name
Wuhan University Journal Of Natural Sciences
Prolactin is a Novel Biochemical Marker in Sera of Iraqi Type-2 Diabetic Women With Metabolic Syndrome in Baghdad.
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Abstract Metabolic syndrome (MS) is a group of clinical and biological abnormalities included risk of insulin resistance , disorders in glucose metabolism , abdominal obesity and abnormal lipid profile these features confer a greater risk of cardiovascular diseases . Anyway, the co-occurrence of diabetes mellitus and metabolic syndrome potentiates the cardiovascular risk associated with each of the two conditions. The present study aimed to determine a relationship between prolactin level in type -2- diabetic Iraqi women and metabolic syndrome, as well to find a relationship between prolactin level and other studied biochemical markers. seventy menopausal diabetic women with metabolic syndrome with age in range (45-50) years were enrolled i

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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
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
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
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
Sat Apr 06 2024
Journal Name
Al- Anbar Medical Journal
Metastatic Ovarian Tumor from Incidental Renal Cell Carcinoma: A Case Report and Literature Review
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