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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 Jan 01 2015
Journal Name
Journal Of Plant Interactions
Photosynthetic and biochemical characterization of in vitro-derived African violet (<i>Saintpaulia ionantha</i>H. Wendl) plants to ex vitro conditions
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Publication Date
Wed Mar 18 2020
Journal Name
International Journal Of Research In Social Sciences And Humanities
THE DILEMMA AND RESISTANCE OF SALMA IN FADIA FAQIRA NOVEL MY NAME IS SALMA
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Publication Date
Mon Jun 01 2009
Journal Name
Engineering And Technology Journal
Synthesis and study of the Novel tetradented ligand type N2O2 and its complexes with (Mn (II) ,Co (II) ,Ni (II) and Cu(II)) ions
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A new Schiff base ligand Bis-1,4-di[N-3-(2-hydroxy-1-amino)- acetophenonylidene] benzylidene [L] and its complexes with (Mn(II) ,Co(II) ,Ni(II and Cu(II)) were synthesized . The ligand was prepared in two steps. In the first step a solution of (terphthalaldehyde) in methanol reacts under reflux with (p-aminoacetophenone) to give an intermediate compound [1-[3-({4-[(3-Acetyl-phenylimino)-methyl]-benzylidene}-amino)-phenyl]- ethanone which reacts in the second step with (2-Amino-phenol) giving the mentioned ligand. The complexes were synthesized by addition the corresponding metal salt solution to the solution of the ligand in methanol under reflux in (1:1) metal to ligand ratio. On the basis of, molar conductance, I.R., UV-Vis, HPLC, chlorid

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Publication Date
Wed Feb 27 2019
Journal Name
Asian Journal Of Chemistry
Estimation of Excess Properties of Binary Liquids Systems of Tetrahydrofurfuryl Alcohol with Short-Chain Carboxylic Acids at 298.15 K
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At the temperature 298.15 K, some physical properties such as: refractive indices (nD), viscosities (η) and densities (ρ) were studied in four liquid-liquid mixtures: carboxylic acids (HCOOH, CH3COOH, CH3CH2COOH and CH3CH2CH2COOH) with tetrahydrofurfuryl alcohol (THFA) with the identified configuration set. These empirical data were utilized to estimate the excess molar volumes (Vm E), refractive index perversions (ΔR), viscosity deviations (ηE) and excess molar Gibbs free energy (ΔG*E). Values of Vm E, ηE , ΔG*E and ΔR were plotted versus mole fraction of tetrahydrofurfuryl alcohol. In all cases, the values of Vm E, ηE , ΔG*E and ΔR that obtained in this study were found to be negative at 298.15 K. The excess parameters

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Publication Date
Wed Apr 12 2017
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
Spectrophotometric Determination of Mefenamic Acid in Pharmaceutical Preparations
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  A simple, accurate and precise spectrophotometric method has been proposed for the determination of Mefenamic acid(MA) in dosage forms. Proposed  method based on the reaction of cited drug with 1,2-Naphthoquinone-4-Sulfonic sodium (NQS). The optimum experimental condition have been studied. Beer's Law is obeyed in the concentration range 0.5-10.0 µg/mL at 450nm with detection limit of 0.189µg/mL.  Effect of pH, reaction time, and volume of NQS on the determination of Mefenamic acid, have been examined. The proposed method has been successfully applied for the determination of  Mefenamic acid in pharmaceutical preparations.
 

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Publication Date
Thu Dec 28 2017
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
Microwave Preparation, Spectral Studies and Antimicrobial Activities Evaluation of Mn(II),Ni(II), Hg(II),Co(II) and Cu(II) Complexes with Schiff Base Ligand
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New Schiff base  and their  Mn(II),Co(II),Ni(II), Cu(II) and Hg(II) complexes formed by the condensation of  O-phathaldehyde and ethylene diamine  (2:1)  to give  ligand (L1) in the first step ,then the ligand (L1) with  2- aminophenol (1:2) to give ligand (L2) were prepared by classic addition through microwave method . These compounds (Ligands and complexes) have been diagnosed electronic spectra, FT-IR, 1H-&13C-NMR (only ligand), magnetic susceptibility, elemental microanalysis and molar conductance measurements. Analytical values displayed that all the complexes appeared (metal: ligand) (1:1) ratio with the six chelation. All the compounds appear a high activity versus four types of bacteria suc

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Publication Date
Wed Apr 19 2017
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
Estimation of Serum Malondialdehyde and Uric acid levels in Smokers and non-Smokers
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  Malondialdehyde (MDA) is one of many low molecular weight end-products of lipid peroxidation; it is as an index of lipid peroxidation. Uric acid is one of the endogenous oxidant-antioxidant paradoxes.        The aim of this study is to evaluate the levels of serum MDA and uric acid in smokers and non smokers.  This study was carried out from January to July 2012 on (30) smokers and (30) non smokers. Serum MDA level was measured spectrophotometrically using thiobarbituric acid method, whereas serum uric acid was measured using enzymatic colorimetric method.      The results of the study revealed a significant increase (P<0.001) in uric acid value in smokers subject

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Publication Date
Sat Dec 30 2023
Journal Name
Iraqi Journal Of Science
On-Site Disposal and Burial of Pit Wastes (Two Southern Iraqi Oil Fields)
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On-site pit is the most common option that may be used to dispose drilling wastes. The contents of these pits vary, depending on the lithology of formations drilled and the drilling mud ,and different chemical additives.
Eighty samples of mud (sludge) and eighty samples of water have been collected from ten pits of two Iraqi oilfields(North Rumaila and South Rumaila/southern Iraq) and were chemically analyzed for metals Cr, Pb,As, Zn, Fe, Mn,K , Na,Ba, Ca, Mg,SO4=,and Cl- in order to determine the quality and quantity content of studied reserve pits
Inefficient equipment, using toxic materials for various drilling processes, absence of regulations for the design and monitoring of pit during and after drilling operation, and leaking

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Publication Date
Fri Sep 22 2017
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
Synthesis A.nd Study The Biological Activity of Some Schiff-Bases Derived F,rom 2- Aminothiazole or 2-Aminobenzothiazole and Vanillin Derivatives
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Two  series    of   1,n-alkylene    glycol   di [4{N(T-thiazolylazo­

nrethinyl)}2-metho y]     phenyl     ether     and     I ,n-alkylene      glycol di[4{N(r-benzo-thiazolylazomethinyl)}2-methoxy]phenyl ether were synthesize-d via rea tions  2-aminothiazole and  2-aminobenzothiazole with  dialdehyde • (which  are synthesized  from  .reaction  vanil.lin with

l ,n-dibromo   or   ehloro.   alkane   in  the   basic   me'dia   )   .  &nb

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Publication Date
Sat Jun 27 2020
Journal Name
Iraqi Journal Of Science
Application of the Electrical Resistivity Method for Site Investigation in University of Anbar, Ar-Ramadi City, Western Iraq
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The 2D resistivity imaging technique was applied in an engineering study for the investigation of subsurface weakness zones within University of Anbar, western Iraq. The survey was carried out using Dipole-dipole array with an n-factor of 6 and a-spacing values of 2 m and 5 m. The inverse models of the 2D electrical imaging clearly show the resistivity contrast between the anomalous parts of the weakness zones and the background resistivity distribution. The thickness and shape of the subsurface weakness zones were well defined from the 2D imaging using Dipole-dipole array of 2 m a-spacing. The thickness of the weakness zone ranges between 9.5 m to 11.5 m. Whereas the Dipole-dipole array with a-spacing of 5 m and n-factor of 6 allocated

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