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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 Jun 30 2013
Journal Name
Al-khwarizmi Engineering Journal
Drilling of FR-4 Composite Materials Using Single Pulse of Nd:YAG Laser
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Laser drilling is capable of producing small, precisely positioned holes with high degree of reproductively. In this paper , IR millisecond Nd:YAG single pulsed laser was used to determine the effect of laser parameters on the drilled hole of the glass - fiber reinforced epoxy composite FR-4 sample of 2 mm in thickness . The type of laser source was GSI lumonics JK760TR Series laser 1.064μm system in a CNC cabin. The JK760TR series has a 0.3-50ms pulse length and a maximum repetition rate 500Hz with an average power of 600W. The investigation of single pulse laser drilling in this paper was based on theoretical and experimental solutions. In single pulse technique, the investigation included focal plane position fpp, pulse shap

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Publication Date
Wed Jan 22 2025
Journal Name
Journal Of Physical Education
Strength Variable Analysis With the Height of Body Mass Center In High Spike Position 4 In Volleyball League Players
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Publication Date
Sun May 10 2020
Journal Name
Baghdad Science Journal
In Silico Analysis of Regulatory Elements of the Vitamin D Receptor
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Vitamin D receptor (VDR) is a nuclear transcription factor that controls gene expression. Its impaired expression was found to be related to different diseases. VDR also acts as a regulator of different pathways including differentiation, inflammation, calcium and phosphate absorption, etc. but there is no sufficient knowledge about the regulation of the gene itself. Therefore, a better understanding of the genetic and epigenetic factors regulating the VDR may facilitate the improvement of strategies for the prevention and treatment of diseases associated with dysregulation of VDR. In the present investigation, a set of databases and methods were used to identify putative functional elements in the VDR locus. Histone modifications, CpG I

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Publication Date
Wed Jun 22 2022
Journal Name
Journal Of Medicinal And Chemical Sciences
Organo-Clay Composites of Intercalated 4-Methylaniline and Its Schiff Base Derivative: Preparation and Characterization
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4-methylaniline and its Schiff base derivative were intercalated into the Bentonite clay interlayers in a solid state reaction followed by a condensation reaction to produce two organo-clay composites. X-ray diffraction was used to identify the changes in basal spacing of montmorillonite layers which exhibited noticeable alteration before and after the formation of the composites. FT-IR spectra, on the other hand, were utilized for identifying the structural compositions of the prepared materials as well as the formation of the intercalated Schiff base derivative. The surface morphology of the composites was examined by Scanning Electron Microscopy SEM and Atomic Force Microscope AFM, which reflected some differences in the surface of prepa

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Publication Date
Mon Jan 01 2018
Journal Name
Aip Conference Proceedings
Fabricated and investigated the structure and super conductivity properties of Bi2Sr2Can-1CunO2n+4+δ compound
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Publication Date
Sun Aug 01 2021
Journal Name
Biochemical And Cellular Archeves
ABILITY OF CRONOBACTER SAKAZAKII FOR ADHESION AND INVASION TO SKG-GT-4 CELL LINE
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ABSTRACT : Fifteenth isolates of C. sakazakii were obtained from previous studies of the sample (infant formula, cerebrospinal fluid and blood). All isolates C. sakazakii identification based on microscopic, biochemical test and confirmed by 16SrRNA. We studied the movement of all isolates and study adhesion to polystyrene plate, adhesion and invasion to Esophageal adenocarcinoma (SKG-GT-4) for four isolates [Cerebrospinal fluid (CSF5), Bloods (B 1), Dialak (A1c), Novolac Allernova (C1)] and its cytotoxicity. Results showed that all isolates can move after 4 hours of incubation and increased after 8 hours, the isolates moved to different distances strong, medium, and weak. The results showed that the number of C. sakazakii colony adherent t

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Publication Date
Sun Mar 07 2010
Journal Name
Baghdad Science Journal
Synthesis, structural study, antimicrobial activity and theoretical treatment of Cr(III), Ni(II), Pt(IV) and Zn(II) complexes with 2-hydroxy-4-Nitro phenyl piperonalidene
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The complexes of the 2-hydroxy-4-Nitro phenyl piperonalidene with metal ions Cr(III), Ni(II), Pt(IV) and Zn(II) were prepared in ethanolic solution. These complexes were characterized by spectroscopic methods, conductivity, metal analyses and magnetic moment measurements. The nature of the complexes formed in ethanolic solution was study following the molar ratio method. From the spectral studies, monomer structures proposed for the nickel (II) and Zinc (II) complexes while dimeric structures for the chromium (III) and platinum (IV) were proposed. Octahedral geometry was suggested for all prepared complexes except zinc (II) has tetrahedral geometry, Structural geometries of these compounds were also suggested in gas phase by using

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Publication Date
Sun Sep 03 2017
Journal Name
Baghdad Science Journal
In Vitro Toxicity Evaluation of Silver Nanoparticles on Entamoeba histolytica trophozoite
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The protozoan parasite Entamoeba histolytica is a causative agent of amoebiasis, where it causes millions of cases of dysentery and liver abscess each year. Metronidazole is a drug of choice against amoebiasis. The drug is a choice because of its efficacy and low cost, but at the same time it causes several adverse side effects; therefore, it is important to find effective medications to treat amoebiasis without any complications or any side effects. The aim of this study is to evaluate the effectiveness of different concentrations (50, 75 and 100 µg/ml) of silver nanoparticle (AgNPs) against trophozoites stages of E. histolytica in vitro. The results showed a significant decrease (p ? 0.05) in numbers of trophozoites stages after treated

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Publication Date
Sun Dec 07 2014
Journal Name
Baghdad Science Journal
Synthesis and Spectral Analysis of Mn (II), Cu (II) ,Ni (II) and Cd (II) Complexes with Mixed Ligands containing 1,10-phenanthroline and Schiff base derived of 4-aminoantipyrine
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The complexes of Schiff base of 4-aminoantipyrine and 1,10-phenanthroline with metal ions Mn (II), Cu (II), Ni (II) and Cd (II) were prepared in ethanolic solution, these complexes were characterized by Infrared , electronic spectra, molar conductance, Atomic Absorption ,microanalysis elemental and magnetic moment measurements. From these studies the tetrahedral geometry structure for the prepared complexes were suggested.The prepared ligand of 4-aminoantipyrine was characterized by using Gc-mass spectrometer .

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Publication Date
Wed Jan 22 2020
Journal Name
Molecules
In Vivo and In Vitro Evaluation of the Protective Effects of Hesperidin in Lipopolysaccharide-Induced Inflammation and Cytotoxicity of Cell
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(1) Background: Plant flavonoids are efficient in preventing and treating various diseases. This study aimed to evaluate the ability of hesperidin, a flavonoid found in citrus fruits, in inhibiting lipopolysaccharide (LPS) induced inflammation, which induced lethal toxicity in vivo, and to evaluate its importance as an antitumor agent in breast cancer. The in vivo experiments revealed the protective effects of hesperidin against the negative LPS effects on the liver and spleen of male mice. (2) Methods: In the liver, the antioxidant activity was measured by estimating the concentration of glutathione (GSH) and catalase (CAT), whereas in spleen, the concentration of cytokines including IL-33 and TNF-α was measured. The in vitro expe

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