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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
Sun Sep 01 2013
Journal Name
Journal Of Baghdad College Of Dentistry
Gingival and Alveolar Ridge Tumor - Like Overgrowth Lesions
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Background: Tumor-like overgrowth lesions of the oral mucosa are pathological growths that project above the normal contour of the oral surface. A practical classification can be made according to the site of origin, the etiology and the histological appearance. The aim of this article is to evaluate and analyze patients with gingival and alveolar ridge tumor-like overgrowth lesions in terms of surgical treatment, diagnosis and outcome. Materials and Methods: Patients complaining of these lesions were treated by surgical excision under local or general anesthesia; the excised lesions were submitted for histopathological examination, during the follow up period the patients were examined for complications and recurrence. Results: Pyogenic gr

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Publication Date
Wed Jun 11 2025
Journal Name
Academic Science Journal
Review Article: Tumor Markers, Types and Clinical Applications
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Over the past ten years, tumor markers have played an increasingly important role in clinicaloncology. This trend is expected to continue as technology advances and our knowledge of thehuman body and disease processes grows. In the treatment of cancer, tumor markers are widelyused for a variety of purposes, including screening, selecting a management strategy,determining the prognosis, and post-therapy follow-up. A comprehensive of the fundamentalsof pathophysiology and identification strategies for each specific malignancy is necessary fortheir prudent application in clinical practice. Oncology's use of cancer biomarkers hastransformed the way that cancer is treated, and led to notable improvements in patient outcomesand cancer tre

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Publication Date
Mon Mar 30 2009
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Prediction of bubble size in Bubble columns using Artificial Neural Network
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In the literature, several correlations have been proposed for bubble size prediction in bubble columns. However these correlations fail to predict bubble diameter over a wide range of conditions. Based on a data bank of around 230 measurements collected from the open literature, a correlation for bubble sizes in the homogenous region in bubble columns was derived using Artificial Neural Network (ANN) modeling. The bubble diameter was found to be a function of six parameters: gas velocity, column diameter, diameter of orifice, liquid density, liquid viscosity and liquid surface tension. Statistical analysis showed that the proposed correlation has an Average Absolute Relative Error (AARE) of 7.3 % and correlation coefficient of 92.2%. A

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Publication Date
Mon May 01 2017
Journal Name
Journal Of Stored Products Research
Detection and prediction of Sitophilus oryzae infestations in triticale via visible and near-infrared spectral signatures
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Triticale is a hybrid of wheat and rye grown for use as animal feed. In Florida, due to its soft coat, triticale is highly vulnerable to Sitophilus oryzae L. (rice weevil) and there is interest in development of methods to detect early-instar larvae so that infestations can be targeted before they become economically damaging. The objective of this study was to develop prediction models of the infestation degree for triticale seed infested with rice weevils of different growth stages. Spectral signatures were tested as a method to detect rice weevils in triticale seed. Groups of seeds at 11 different levels (degrees) of infestation, 0–62%, were obtained by combining different ratios of infested and uninfested seeds. A spectrophotometer wa

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Publication Date
Fri May 01 2020
Journal Name
Journal Of Engineering
Semi-Analytical Prediction of Flank Tool Wear in Orthogonal Cutting of Aluminum
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This study aims to model the flank wear prediction equation in metal cutting, depending on the workpiece material properties and almost cutting conditions. A new method of energy transferred solution between the cutting tool and workpiece was introduced through the flow stress of chip formation by using the Johnson-Cook model. To investigate this model, an orthogonal cutting test coupled with finite element analysis was carried out to solve this model and finding a wear coefficient of cutting 6061-T6 aluminum and the given carbide tool.

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Publication Date
Sun May 05 2024
Journal Name
Technium Business And Management
Measuring Blue Ocean Leadership activities in public organizations: field research in the Ministry of Communications
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This study aims to identify the level of application of blue ocean leadership activities in public organizations and to build a conceptual and cognitive framework around this concept. The study adopted a descriptive-analytical approach, and the research sample consisted of (95) individuals from the senior management working at the center of the Iraqi Ministry of Communications (director general, department manager, section head). The data analysis technique used is structural equation modeling (SEM) and the Statistical Package for the Social Sciences (SPSS). The results indicate that the senior management in the Ministry of Communications is working to adopt the blue ocean leadership style through its activities, but not to the leve

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Publication Date
Sun Dec 01 2019
Journal Name
Saudi Medical Journal
The diagnostic power of circulating micro ribonucleic acid 34a in combination with cancer antigen 15-3 as a potential biomarker of breast cancer
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Publication Date
Wed Mar 15 2023
Journal Name
Bionatura
Study the antioxidant of Matricaria chamomilla (Chamomile) powder: In vitro and vivo
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Oxidative stress is oxidative damage caused by free radicals and reactive oxygen species (ROS). These ROS can cause oxidative damage to cellular components, including membrane lipids, receptors, enzymes, proteins, and nucleic acids. It would eventually lead to cell apoptosis and the appearance of certain pathological conditions. This work investigates the antioxidant potentials of chamomile extract in vitro by evaluating the extract activity to scavenge 2,2-Diphenyl-1-picrylhydrazyl (DPPH), also in vivo by investigating its effects on oxidative stress-induced rats by assessing the total oxidant status (TOS) and total antioxidant capacity in the radiation exposed rats with and without the treatment with chamomile extract. The results

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Publication Date
Wed Mar 25 2020
Journal Name
International Journal Of Drug Delivery Technology
Preparation, Characterization and In-Vitro Diffusion Study of Different Topical Flurbiprofen Semisolids
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Flurbiprofen (FLB) is chemically 2-(3- fluoro-4-phenyl phenyl) propanoic acid. It is a nonsteroidal anti-inflammatory drug (NSAID) used in the treatment of rheumatoid arthritis and osteoarthritis. Oral administration of this drug is associated with severe gastrointestinal side effects like ulceration and gastrointestinal bleeding. The solution to this problem lies in the fact that topically applied NSAIDs are safer than orally. This study aims to prepare different topical semisolid formulation of FLB as cream base (o/w), (w/o) and gel base using different gel-forming agents in different concentrations. Comparing characterization properties in addition to release and diffusion study for all the prepared formulas to select the best on

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Publication Date
Wed Mar 10 2021
Journal Name
Baghdad Science Journal
The frequency of IgM-anti HAV in the sera of patients with hepatitis in Iraq
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Three hundred and fifty five patients with hepatitis were investigated in this study all cases gave negative result with HBs Ag , IgM-anti HCV , IgM-anti HEV, IgM-anti HDV and anti-HIV tests . The frequency of IgM-anti HAV was 113 and the percentage was 32 % in all ages but when these patients divided into five groups dependent on ages. The highest percentage of IgM-anti HAV was (45%) in age <10 and the percentage declined with age increase till to 9% in age >41 year.

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