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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 Apr 03 2025
Journal Name
Journal Of The American Oil Chemists' Society
A novel deep eutectic solvent‐based liquid membrane for the extraction of glycerol from crude biodiesel
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Abstract<p>This study used deep eutectic solvent (DES) as the liquid membrane in a bulk liquid membrane system (BLM) to remove glycerol from waste cooking oil‐based biodiesel. The DES was prepared from choline chloride and tetraethylene glycol at a molar ratio of 1:5. Diethyl ether was employed as a novel strip phase for the glycerol in BLM. The effects of the DES: biodiesel ratio, stirring speed, and extraction time on the extraction and stripping efficiencies were investigated. The results showed that BLM could give better glycerol removal from biodiesel than mechanical shaking. Increasing the DES: biodiesel ratio, stirring speed, and extraction time can enhance glycerol removal from the feed phase, achievi</p> ... Show More
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Publication Date
Tue Sep 01 2015
Journal Name
Journal Of Engineering
Application of Box-Behnken Method Based ANN-GA to Prediction of wt.% of Doping Elements for Incoloy 800H Coated by Aluminizing-Chromizing
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In this work , an effective procedure of Box-Behnken based-ANN (Artificial Neural Network) and GA (Genetic Algorithm) has been utilized for finding the optimum conditions of wt.% of doping elements (Ce,Y, and Ge) doped-aluminizing-chromizing of Incoloy 800H . ANN and Box-Behnken design method have been implanted for minimizing hot corrosion rate kp (10-12g2.cm-4.s-1) in Incoloy 800H at 900oC . ANN was used for estimating the predicted values of hot corrosion rate kp (10-12g2.cm-4.s-1) . The optimal wt.% of doping elements combination to obtain minimum hot corrosion rate was calculated using genetic alg

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Publication Date
Thu Jun 27 2024
Journal Name
Iraqi Journal Of Pharmaceutical Sciences( P-issn 1683 - 3597 E-issn 2521 - 3512)
Impact of Gliclazide Modified Release or Glimepiride as Add-on Therapy to Metformin on Glycemic and Oxidative Stress Parameters in Type 2 Diabetic Patients
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Background: Type 2 diabetes mellitus is a condition characterized by an elevation of oxidative stress, which has been implicated in diabetic progression and its vascular complications. Aim: Assessing the impact of gliclazide modified release (MR) versus glimepiride on oxidative stress markers, glycemic indices, lipid profile, and estimated glomerular filtration rate in uncontrolled type 2 diabetic patients on metformin monotherapy. Methods: This was an observational comparative study conducted in Thi-Qar specialized diabetic, endocrine, and metabolism center. Sixty-six patients were randomized into two groups based on the addition of the sulfonylureas (SUs). Group 1 (33 patients) was on gliclazide MR, whereas Group 2 (33 patients)

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Publication Date
Fri May 10 2019
Journal Name
Research Journal Of Chemistry And Environment
Solid Phase Extraction of Theophylline in Aqueous Solutions by Modified Magnetic Iron Oxide Nanoparticles as an Extractor Material and Spectrophotometry Technique for the Determination
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new, simple and fast solid-phase extraction method for separation and preconcentration of trace theophylline in aqueous solutions was developed using magnetite nanoparticles (MIONPs) coated with aluminium oxide (AMIONPs) and modified with palmitate (P) as an extractor (P@AMIONPs). It has shown that the developed method has a fast absorbent rate of the theophylline at room temperature. The parameters that affect the absorbent of theophylline in the aqueous solutions have been investigated such as the amount of magnetite nanoparticle, pH, standing time and the volume, concentration of desorption solution. The linear range, limit of quantification (LOQ) and limit of detection (LOD) for the determination of theophylline were 0.05-2.450 μg mL-

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Publication Date
Fri Jan 01 2021
Journal Name
Journal Of Engineering
A Proposed Adaptive Bitrate Scheme Based on Bandwidth Prediction Algorithm for Smoothly Video Streaming
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A robust video-bitrate adaptive scheme at client-aspect plays a significant role in keeping a good quality of video streaming technology experience. Video quality affects the amount of time the video has turned off playing due to the unfilled buffer state. Therefore to maintain a video streaming continuously with smooth bandwidth fluctuation, a video buffer structure based on adapting the video bitrate is considered in this work. Initially, the video buffer structure is formulated as an optimal control-theoretic problem that combines both video bitrate and video buffer feedback signals. While protecting the video buffer occupancy from exceeding the limited operating level can provide continuous video str

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Publication Date
Wed May 03 2023
Journal Name
Periodicals Of Engineering And Natural Sciences (pen)
Enhancing smart home energy efficiency through accurate load prediction using deep convolutional neural networks
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The method of predicting the electricity load of a home using deep learning techniques is called intelligent home load prediction based on deep convolutional neural networks. This method uses convolutional neural networks to analyze data from various sources such as weather, time of day, and other factors to accurately predict the electricity load of a home. The purpose of this method is to help optimize energy usage and reduce energy costs. The article proposes a deep learning-based approach for nonpermanent residential electrical ener-gy load forecasting that employs temporal convolutional networks (TCN) to model historic load collection with timeseries traits and to study notably dynamic patterns of variants amongst attribute par

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Publication Date
Thu Sep 01 2016
Journal Name
Physica Medica
Quantitative analysis of sentinel lymph node detection using a novel small field of view hybrid gamma camera (HGC)
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Introduction The Hybrid Gamma Camera (HGC) is being developed to enhance the localisation of radiopharmaceutical uptake in targeted tissues during surgical procedures such as sentinel lymph node (SLN) biopsy. Purpose To assess the capability of the HGC, a lymph-node-contrast (LNC) phantom was constructed for an evaluative study simulating medical scenarios of varying radioactivity concentration and SLN size. Materials and methods The phantom was constructed using two methyl methacrylate PMMA plates (8 mm thick). The SLNs were simulated by drilling circular wells of diameters ranging between 10 mm and 2.5 mm (16 wells in total) in one plate. These simulated SLNs were placed underneath scattering material with thicknesses ranging between 5 mm

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Publication Date
Sat Dec 30 2023
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Kinetic Modeling of Electromembrane Extraction of Copper using a Novel Electrolytic Cell Provided with a Supported Liquid Membrane
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   The aim of this study is to investigate the kinetics of copper removal from aqueous solutions using an electromembrane extraction (EME) system. To achieve this, a unique electrochemical cell design was adopted comprising two glass chambers, a supported liquid membrane (SLM), a graphite anode, and a stainless-steel cathode. The SLM consisted of a polypropylene flat membrane infused with 1-octanol as a solvent and bis(2-ethylhexyl) phosphate (DEHP) as a carrier. The impact of various factors on the kinetics constant rate was outlined, including the applied voltage, initial pH of the donor phase solution, and initial copper concentration. The results demonstrated a significant influence of the applied voltage on enhancing the rate of c

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Publication Date
Wed Jan 02 2019
Journal Name
International Journal Of Agricultural & Statistical Sciences
RESPONSE OF OLIVE SEEDLINGS TO HUMIC ACID AND INOCULATION BY FUNGI (TRICHODERMA SSP) AND THE INTERACTION OF THEM AND IRRIGATION BY SALT WATER ON VEGETATIVE GROWTH.
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Publication Date
Sat Feb 28 2026
Journal Name
Journal Of Baghdad College Of Dentistry
Immunohistochemical expression of ICAM-1 and Cortactin as cell adhesive molecule and invasive markers in Hodgkin’s and non-Hodgkin’s lymphoma of the head and neck region (A comparative study)
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Background: Lymphomas are a group of diseases caused by malignant lymphocytes that accumulate in lymph nodes and cause the characteristic clinical features of lymphadenopathy. Intercellular adhesion molecule-1 (ICAM-1) (CD54) is a transmembrane glycoprotein belonging to the immunoglobulin superfamily of adhesion molecules. Cortactin was first identified as one of the major substrates for src kinase. because it localized to Cortical actin structures, The aims of this study was to evaluate and compare the immunohistochemical of ICAM-1 expression as cell adhesion molecule marker and Cortactin expression as invasive marker. Material and Methods: This study was performed on (68) formalin-fixed, paraffin-embedded blocks, histopathologically diagn

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