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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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Sat Oct 01 2022
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Sat Sep 05 2020
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Al-kindy College Medical Journal
Evaluation Aseptic Loosening of Primary Hip Arthroplasty
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Publication Date
Thu Mar 01 2018
Journal Name
Journal Of Engineering
Tribological Characteristics Evaluation of Mustard Oil Blends
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A progressive increase in the desire for environmentally friendly lubricants by users and strict government regulations for the use of these lubricants has provided an opportunity to use plant oils as biodegradable lubricants, therefore vegetable oils have been investigated to replace oil lubricants because of their maintaining the conditions of nature (environment) properties. In this paper, the influences of the blending ratio of mustard seeds oil with commercial mineral oil (SAE40) on the tribological characteristics were investigated and compared with mineral oil using the four-ball tribotester. Mustard seeds oil was blended with mineral oil at a volumetric ratio ranging from 22.5 to 90%. All experimental works were

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Publication Date
Sat Sep 05 2020
Journal Name
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Evaluation Aseptic Loosening of Primary Hip Arthroplasty
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Background : The number of primary hip arthroplasty is growing with every passing year. At present this surgical operation has no equal in the rate of yielding good results. Despite the fact that in many cases in the long term after surgery radiolucent lines around the cup are observed, the clinical outcomes remain satisfactory.
Aim of the study :To study the clinical and radiological manifestations of the aseptic loosening of the endoprosthesis
Methods: This is a prospective study based on an analysis of diagnostic findings of 51 patients with aseptic loosening of hip joint components, aged 30 to 84 years. We depend for diagnosis of a septic losing by both clinical evaluation and X-ray assessment Results:The majority of clinical a

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Publication Date
Thu May 01 2025
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Electromembrane extraction of Cadmium (II) using a novel design of electrochemical cell with a flat sheet supported liquid membrane
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Publication Date
Sun Jun 05 2016
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A novel online coupling of ion selective electrode with the flow injection system for the determination of vitamin B1
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A simple, fast, selective of a new flow injection analysis method coupled with potentiometric detection was used to determine vitamin B1 in pharmaceutical formulations via the prepared new selective membranes. Two electrodes were constructed for the determination of vitamin B1 based on the ion-pair vitamin B1-phosphotungestic acid (B1-PTA) in a poly (vinyl chloride) supported with a plasticized di-butyl phthalate (DBPH) and di-butyl phosphate (DBP). Applications of these ion selective electrodes for the determination of vitamin B1 in the pharmaceutical preparations for batch and flow injection systems were described. The ion selective membrane exhibited a near-Nernstian slope values 56.88 and 58.53 mV / decade, with the linear dy

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Sat Jan 01 2022
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Publication Date
Wed Mar 01 2023
Journal Name
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Publication Date
Tue Feb 26 2019
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Sun Jun 20 2021
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Performance Evaluation of Intrusion Detection System using Selected Features and Machine Learning Classifiers
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Some of the main challenges in developing an effective network-based intrusion detection system (IDS) include analyzing large network traffic volumes and realizing the decision boundaries between normal and abnormal behaviors. Deploying feature selection together with efficient classifiers in the detection system can overcome these problems.  Feature selection finds the most relevant features, thus reduces the dimensionality and complexity to analyze the network traffic.  Moreover, using the most relevant features to build the predictive model, reduces the complexity of the developed model, thus reducing the building classifier model time and consequently improves the detection performance.  In this study, two different sets of select

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