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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 Aug 01 2016
Journal Name
2016 38th Annual International Conference Of The Ieee Engineering In Medicine And Biology Society (embc)
Changes in the EEG amplitude as a biomarker for early detection of Alzheimer's disease
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The rapid increase in the number of older people with Alzheimer's disease (AD) and other forms of dementia represents one of the major challenges to the health and social care systems. Early detection of AD makes it possible for patients to access appropriate services and to benefit from new treatments and therapies, as and when they become available. The onset of AD starts many years before the clinical symptoms become clear. A biomarker that can measure the brain changes in this period would be useful for early diagnosis of AD. Potentially, the electroencephalogram (EEG) can play a valuable role in early detection of AD. Damage in the brain due to AD leads to changes in the information processing activity of the brain and the EEG which ca

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Publication Date
Wed Jun 28 2023
Journal Name
Iraqi Journal Of Market Research And Consumer Protection
PREPARATION OF A COMBINATION OF NANO- MEDICINAL PLANTS AS ANTIOXIDANTS AND MICROORGANISMS: PREPARATION OF A COMBINATION OF NANO- MEDICINAL PLANTS AS ANTIOXIDANTS AND MICROORGANISMS
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ABSTRACT

            The controversy is currently revolving around industrial additives, including antioxidants, their negative effects on consumer health and the emergence of various and various diseases, which led scientists and researchers to intensify most studies on natural antioxidants and their synthesis from medicinal plants mentioned in ancient medicine and in divine books as potential antioxidants of increasing importance. Therefore, this study was designed to synthesize silver nitrate particles from plant leaf extracts (Figs, Olives, and Moringa) and study their effect on bacterial inhibition of each of the undesirable Coliform bacteria (E-Coli,

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Publication Date
Thu Feb 16 2023
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
A Novel Single Nucleotide Polymorphism of Interleukin-10 Gene is Linked to Type 2 Diabetes Mellitus in Iraqi Patients with Toxoplasmosis(Conference Paper )#
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Type 2 diabetes mellitus (T2DM) is a chronic disorder that is a serious health concern all over the globe, it is linked to Interleukin-10 (IL-10) single nucleotide polymorphisms (SNPs) at the promoter region. On the other hand, diabetes influences the cellular and humoral immunity predisposing the patient to a variety of opportunistic parasites one of them is Toxoplasma gondii (T. gondii), which may infect any nucleated cell, including pancreatic cells. The purpose of this research was to explore the association of IL-10 genetic polymorphisms with T2DM and latent toxoplasmosis among Iraqi patients with T2DM. Fifty-five and fifty-eight venous blood samples were taken from T2DM patients and age-matched non-diabetic person

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Publication Date
Wed Aug 01 2018
Journal Name
Ecotoxicology And Environmental Safety
Biochemical and molecular alterations in freshwater mollusks as biomarkers for petroleum product, domestic heating oil
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Publication Date
Wed Aug 30 2023
Journal Name
Al-kindy College Medical Journal
Serum Pseudocholinesterase as a Biomarker in the Differentiation between Gastric Cancer and Benign Gastric Diseases
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Background: Worldwide gastric cancer is the fifth most common cancer with poor prognosis. In early stages, it is hard to distinguish gastric cancer from benign gastric diseases, resulting in delayed diagnosis. There is a need to develop a biomarker for differentiating between gastric cancer and benign gastric diseases. Serum cholinesterase is synthesized in liver and released into plasma, and it has an important role in oncogenesis.

Objectives: To determine the correlation between serum cholinesterase activity and gastric cancer, in comparison to benign gastric diseases.

Subjects and Methods: A case control study carried out at Medical City Direct

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Publication Date
Mon Jul 10 2023
Journal Name
Journal Of Engineering
Rhythm As Creative System In Houses Architecture Comparative Application Study Between Heritage And Contemporary Houses
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Rhythm is considered one of the creative concepts in the recent architectural thought; it has emerged clearly as a mean of creating the highest levels of creativity in architecture, especially in contemporary architectural movements. The importance of rhythm has  emerged, especially, when the architecture , its beginnings concentrated on the principle of the links with poetic structures. Many architectural studies deal with concept of rhythm in architecture with different ways various according to the trend of each study, this show the importance of studying the concept of rhythm in the architectural field in general. This study try to focus on the utilization of rhythm as creative system in architecture of heritage and contemporary

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Publication Date
Thu Jun 15 2023
Journal Name
Journal Of Baghdad College Of Dentistry
Evaluation of leukocytes cells types counts in blood from patients with different severities of periodontal diseases
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Background: Periodontal diseases are inflammatory disorders caused by the accumulation of oral biofilm and the host response to this accumulation which characterized by exaggerated leukocytes and neutrophils attraction to the sites of inflammation by chemoattractants which are a very important part of the pathogenesis of periodontal diseases. This study aimed to determine and compare the clinical periodontal parameters and the leukocyte cell types in the peripheral blood between patients with gingivitis and periodontitis with different severities compared to healthy controls. Materials and methods: This study included 150 male subjects aged between 35-50 years. They were divided into three groups: gingivitis group (n=30), periodontitis p

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Publication Date
Sat Mar 01 2014
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
Strategic Performance Evaluation Using Benchmarking Technique: Applied Research In The Sample Of Offices Of Inspectors General
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In light of the rapid changes in the business environment and the entry of administrative leaders in the challenges of the atheist and twenty- increasing competition between sectors and the desire to acquire the skills, the traditional methods are no longer viable, which requires doing evaluates performance according to a more holistic, rather than limiting the performance evaluation on the financial hub that has not longer enough alone, as well as benchmarking method that has proven successful in developed countries as a way to develop and improve products and services.

I've touched your search to the development of indicators evaluating the performance and preparation of a mechanism for making comparisons of reference between o

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Publication Date
Fri Jun 17 2022
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Evaluation the Effectiveness of Phenolic Compound of Salvia Frigida on Induced Atopic Dermatitis in Experimental Mice
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Abstract

To evaluate the effectiveness of Phenolic Compound of Salvia Frigida on induced atopic dermatitis (AD) of mice. Forty mice were included in the study, divided in to four groups (10 mice/group): apparently healthy, induced AD without treatment, induced AD treated with tacrolimus 0.1% ointment, and induced AD treated with Phenolic Compound of Salvia Frigida cream 5%. Examination of histopathology was done and skin homogenates levels also measured. Levels of WBC, Eosinophil, skin tissue homogenate of IL-13 and IL-4, serum IgE, and histopathological scores were significantly increased among induced non treated AD group in comparison with control group. Comparisons of non-treated induced AD

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Publication Date
Tue Jan 12 2021
Journal Name
Systematic Review In Pharmacy
CUPPER(||)AND MERCURY (||)Complexes WITH SCHIFF BASE LIGAND FROM BENZIDIN WITH ISATIN AND BENZOIN:SYNTHESIS,SPECTRAL CHARACTERIZATION, THERMAL STUDIES AND BIOLOGICAL ACTIVITIES
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CUPPER(||)AND MERCURY (||)Complexes WITH SCHIFF BASE LIGAND FROM BENZIDIN WITH ISATIN AND BENZOIN:SYNTHESIS,SPECTRAL CHARACTERIZATION, THERMAL STUDIES AND BIOLOGICAL ACTIVITIES