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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
Wed Dec 15 2004
Journal Name
Iraqi Journal Of Laser
Low Power He:Ne Laser Radiation in Killing Photosensitized Helicobacter pylori in Vitro
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Four photosensitizers were used to test inhibitory effect of Helicobacter pylori bacteria using
low power helium: neon red laser radiation. Biopsies were collected from 176 patients and H. pylori were
isolated, identified and bacterial suspension was prepared. Samples of this suspension were mixed with
various low concentrations of the test sensitizer. The mixture samples were exposed to different laser
radiation doses. The samples were then inoculated and the inhibition zones were studied and compared
with their analogues of control samples. The most effective sensitizer with optimum concentration and
irradiation dose was determined. Statistical analysis of results was performed. The sensitizers' toluidine
blue and

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Publication Date
Thu May 18 2023
Journal Name
Journal Of Engineering
Prediction of Coefficient of Permeability of Unsaturated Soil
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A simple technique is proposed in this paper for estimating the coefficient of permeability of an unsaturated soil based on physical properties of soils that include grain size analysis, degree of saturation or water content, and porosity of the soil. The proposed method requires the soil-water characteristic curve for the prediction of the coefficient of permeability as most of the conventional methods. A procedure is proposed to define the hydraulic conductivity function from the soil water characteristic curve which is measured by the filter paper method. Fitting methods are applied through the program (SoilVision), after indentifying the basic properties of the soil such as Attereberg limits, specific gravity, void ratio, porosity, d

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Publication Date
Sun Dec 01 2013
Journal Name
Bmc Complementary And Alternative Medicine
Synergy of antibacterial and antioxidant activities from crude extracts and peptides of selected plant mixture
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Abstract<sec><title>Background

A plant mixture containing indigenous Australian plants was examined for synergistic antimicrobial activity using selected test microorganisms. This study aims to investigate antibacterial activities, antioxidant potential and the content of phenolic compounds in aqueous, ethanolic and peptide extracts of plant mixture.

Methods

Well diffusion, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays were used to test antibacterial activity against four pathogenic bacteria namelyStaphylococcus aureus, Escherichia coli, Bacil

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Publication Date
Thu Sep 08 2022
Journal Name
Al-khwarizmi Engineering Journal
Performance Prediction in EDM Process for Al 6061 Alloy Using Response Surface Methodology and Genetic Algorithm
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The Electric Discharge (EDM) method is a novel thermoelectric manufacturing technique in which materials are removed by a controlled spark erosion process between two electrodes immersed in a dielectric medium. Because of the difficulties of EDM, determining the optimum cutting parameters to improve cutting performance is extremely tough. As a result, optimizing operating parameters is a critical processing step, particularly for non-traditional machining process like EDM. Adequate selection of processing parameters for the EDM process does not provide ideal conditions, due to the unpredictable processing time required for a given function. Models of Multiple Regression and Genetic Algorithm are considered as effective methods for determ

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Publication Date
Fri Sep 26 2025
Journal Name
Applied Data Science And Analysis
Deep Learning in Genomic Sequencing: Advanced Algorithms for HIV/AIDS Strain Prediction and Drug Resistance Analysis
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Genome sequencing has significantly improved the understanding of HIV and AIDS through accurate data on viral transmission, evolution and anti-therapeutic processes. Deep learning algorithms, like the Fined-Tuned Gradient Descent Fused Multi-Kernal Convolutional Neural Network (FGD-MCNN), can predict strain behaviour and evaluate complex patterns. Using genotypic-phenotypic data obtained from the Stanford University HIV Drug Resistance Database, the FGD-MCNN created three files covering various antiretroviral medications for HIV predictions and drug resistance. These files include PIs, NRTIs and NNRTIs. FGD-MCNNs classify genetic sequences as vulnerable or resistant to antiretroviral drugs by analyzing chromosomal information and id

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Publication Date
Sun Mar 01 2015
Journal Name
Baghdad Science Journal
Study the effect of Aqueous cold water and Alcoholic extracts of Ziziphus spina christi against bacteria isolated from Conjunctivitis In vitro and In vivo
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This study aimed to study the effect of Ziziphus spina christi Aqueous cold and Alcoholic leaves and fruits extracts on the growth and activities of the following types of bacteria :( Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Streptococcus pyogenes ). The results appeared outweigh the alcoholic extract of leaves and fruits of Sidr that prepared by saxholate extractor by addition of ethanol 95% significant superiority as compared with aqueous extract that prepared by using distilled water as was its influence inhibitor to the growth and effectiveness of bacteria , about the treatment of in-vivo to cause injury to these types of bacteria diagnosed laboratory mice and treated with alcoholic extract of the leaves o

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Publication Date
Sat Jan 01 2022
Journal Name
Lecture Notes In Civil Engineering
Evaluation the Level of Service of Signalized Intersection: Al-Amreia Intersection as a Case Study
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Abstract<p>One of the main element in the network is the intersection which consider as the critical points because there are many conflict in this element. The capability and quality of operation of an intersection was assessed to provide a better understanding of the network's traffic efficiency. In Baghdad city, the capital of/Iraq the majority of the intersections are operated under the congestion status and with level of service F, therefore theses intersection are consider as high spot point of delay in the network of Baghdad city. In this study we selected Al-Ameria signalized intersection as a case study to represent the delay problem in the intersections in Baghdad. The intersection is located in the w</p> ... Show More
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Publication Date
Fri Apr 05 2024
Journal Name
Tikret Journal Of Agricultural Sciences
Effect of adding Humic acid and spraying Boric acid on Growth and Yield of cauliflower Brassica oleracea var. botrytis
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Publication Date
Mon Mar 08 2021
Journal Name
Baghdad Science Journal
Synthesis and Characterization of N-((6-substituted - Benzothiazol-2-Y)succunamic acid.3-(6-substituted-benzothiazol-2-Y1)-Carbamoyl Prorionyl Chloride and study of thier Biological effects
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Twelve N-(6-sustirured benzothanol-2-y1) succinamic acids and 3-(6-substitted benzonathol-2-y1)-carbamoyl propionyl chloride were synthesized in good yields from reaction of benzonathol2-yl)

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Publication Date
Thu Nov 29 2018
Journal Name
Al-khwarizmi Engineering Journal
Surface Roughness Prediction for Steel 304 In Edm Using Response Graph Modeling
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Electrical Discharge Machining (EDM) is a non-traditional cutting technique for metals removing which is relied upon the basic fact that negligible tool force is produced during the machining process. Also, electrical discharge machining is used in manufacturing very hard materials that are electrically conductive. Regarding the electrical discharge machining procedure, the most significant factor of the cutting parameter is the surface roughness (Ra). Conventional try and error method is time consuming as well as high cost. The purpose of the present research is to develop a mathematical model using response graph modeling (RGM). The impact of various parameters such as (current, pulsation on time and pulsation off time) are studied on

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