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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
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
Sun Sep 01 2019
Journal Name
Transylvanian Review
Metacongnitive Thinking Skills Implied in Questions and Activities of Computer Textbook for the Fifth Grade Preparatory
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The research aims to know the availability of supra-cognitive thinking skills in the questions and activities of the computer book for the fifth grade preparatory scientific and literary branches in Iraq for the academic year 2018/2019, as the researcher has prepared a list of supra-cognitive thinking skills included two areas and (6) key skills and (27) A sub - skill, where by the questions and activities of the aforementioned authors were analyzed. The researcher followed the descriptive analytical approach "method of content analysis", and adopted the explicit and implicit unit of analysis, as was verified the validity and stability of the analysis, and the results showed unevenness and imbalance in the distribution of supra-cognitive th

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Publication Date
Tue Aug 01 2023
Journal Name
Dna Repair
The interactions between DNA methylation machinery and long non-coding RNAs in tumor progression and drug resistance
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DNA methylation is one of the main epigenetic mechanisms in cancer development and progression. Aberrant DNA methylation of CpG islands within promoter regions contributes to the dysregulation of various tumor suppressors and oncogenes; this leads to the appearance of malignant features, including rapid proliferation, metastasis, stemness, and drug resistance. The discovery of two important protein families, DNA methyltransferases (DNMTs) and Ten-eleven translocation (TET) dioxygenases, respectively, which are responsible for deregulated transcription of genes that play pivotal roles in tumorigenesis, led to further understanding of DNA methylation-related pathways. But how these enzymes can target specific genes in different malignancies;

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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
Wed Dec 01 2021
Journal Name
Baghdad Science Journal
Using Fuzzy Clustering to Detect the Tumor Area in Stomach Medical Images
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Although the number of stomach tumor patients reduced obviously during last decades in western countries, but this illness is still one of the main causes of death in developing countries. The aim of this research is to detect the area of a tumor in a stomach images based on fuzzy clustering. The proposed methodology consists of three stages. The stomach images are divided into four quarters and then features elicited from each quarter in the first stage by utilizing seven moments invariant. Fuzzy C-Mean clustering (FCM) was employed in the second stage for each quarter to collect the features of each quarter into clusters. Manhattan distance was calculated in the third stage among all clusters' centers in all quarters to disclosure of t

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Publication Date
Fri Jan 01 2016
Journal Name
Iraqi Journal Of Agricultural Sciences
Study the effect of cytokinins and auxins in the composition and production of In Vitro plantlets Hippeastrum Hybridum
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Publication Date
Mon Jan 01 2024
Journal Name
Kafkas Universitesi Veteriner Fakultesi Dergisi
Assessment of In-vitro Cytotoxicity and In-ovo Virucidal Antiviral Efficacy of Various Plant Extracts and Bioactive Molecules
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Publication Date
Tue Mar 28 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Phytochemical Study of Cynara scolymus L. (Artichoke) (Asteraceae) Cultivated in Iraq, Detection and Identification of Phenolic Acid Compounds Cynarin and Chlorogenic Acid
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The leaves of globe artichoke, Cynara scolymus Family Asteraceae/ compositea have long – used in traditional medicine and now included in British and European Pharmacopeia, the British Harbal Pharmacopeia and complete German Commission E monographs.The plant originally comes from Mediterranean region and North Africa and cultivated around the world. The flowers are used worldwide for nutrition purposes and the leaves for medical purposes including hepatic affections. The plant wildly distributed in Iraq in the watery lines and boundary of the field.The plant contains many phytochemicals such as the bitter phenolic acids whose choleretic and hypocholestremic as these compounds are antioxidant. Other materials to h

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Publication Date
Sun Dec 01 2013
Journal Name
Political Sciences Journal
Activities of International Studies Branch
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نشاطات فرع الدراسات الدولية

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