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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
Sat Sep 01 2018
Journal Name
J Of Baghdad College Of Dentistry
Serum Tumor Necrosis Factor Alpha and High Sensitive C-Reactiveprotein as Biomarkersin Periodontitis in Iraqi Patients with Osteoarthritis
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Publication Date
Sun Apr 01 2018
Journal Name
Al–bahith Al–a'alami
‏Framing war against ISIS in New York Times/ from 10/17/2016 to 4/16/2017
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The research is aimed at investigating how the New York Times framed the war against ISIS in its news coverage and which news sources it adopted while reporting on this war.
‏ The research could be classified under descriptive researches. The survey methodology has been adopted and the content analysis has been used. The research sample consists of all the news stories the New York Times have published about the war against ISIS from 10/17/2016 to 4/16/2017 according to the comprehensive sampling method. The number of news stories that were analyzed was (155) news story. The research tool was (coding scheme).
The research has reached the following conclusions:
‏ 1. In its news coverage of the war against ISIS, the New York T

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Publication Date
Wed Jan 01 2014
Journal Name
International Journal Of Advanced Research
Evaluation of anti-Helicobacter pylori IgG level in the serum of patients with Rheumatoid arthritis
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Rheumatoid arthritis is an inflammatory chronic disease with an autoimmune pathogenesis. To determine the role of Helicobacter pylori as a trigger agent, twenty five patients with rheumatoid arthritis of ages (15-47) years have been investigated and compared with twenty healthy individuals. All the studied groups were carried out to measure the rheumatoid arthritis (RA) IgM, anti-CCP antibody IgG and IgA by ELISA test and by measured anti-IgG antibody level of H. pylori by using ELISA and IFAT techniques. The present study showed significant differences (P< 0.05) of anti-H. Pylori in sera of RA patients than control group, this lead to suggest that H. pylori had a role in pathogenesis of RA.

Publication Date
Thu Jan 01 2015
Journal Name
World Journal Of Experimental Biosciences
Evaluation of anti-Helicobacter pylori antibodies level in sera of patients with chronic hepatitis B
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The relationship between chronic hepatitis B virus and Helicobacter pylori infection was evaluated to determine, seventy five patients with chronic hepatitis B infection (8-70 years) were investigated. The results were compared with the results of 50 healthy volunteers. Anti-H. pylori antibodies IgA and IgG were measured by Indirect fluorescent antibody test (IFAT) in sera of patients and healthy groups. The percentage of anti-H.pylori IgA antibodies (26.67%) were significantly (P<0.01) higher than healthy control group. While, no significant difference was found between the percentages of anti-H. pylori IgG antibodies (48 %) in patient sera and these kind of antibodies in sera of healthy control group (P > 0.05). The present results indica

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Publication Date
Tue May 13 2014
Journal Name
International Journal Of Chemical And Process Engineering Research
SYNTHESIS, PHYSICO-CHEMICAL AND ANTIMICROBIAL PROPERTIES OF SOME METAL (II) -MIXED LIGAND COMPLEXES OF TRIDENTATE SCHIFF BASE DERIVES FROM Β-LACTAM ANTIBIOTIC {(CEPHALEXIN MONO HYDRATE)-4-CHLOROBENZOPHENONE} AND SACCHARIN
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A new Schiff base (4-chlorophenyl)(phenyl methanimine (6R,7R)-3-methyl-8-oxo-7-(2-phenylpropanamido)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate=HL=C29H24ClN3O4S) has been synthesized from β-lactam antibiotic (cephalexin mono hydrate (CephH)=(C16H19N3O5S.H2O) and 4- chlorobenzophenone. Metal mixed ligand complexes of the Schiff base were prepared from chloride salt of Fe(II), Co(II), Ni(II), Cu(II), Zn(II) and Cd(II), in 50% (v/v) ethanol – water medium in aqueous ethanol(1:1) and Saccharin(C7H5NO3S) containing sodium hydroxide. Several physical tools in particular; IR, C:H:N , 1H NMR,13C NMR for ligand, melting point, molar conductance, magnetic moment. and determination of the percentage of the metal in the complexes by flame(AAS

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Publication Date
Wed Jan 01 2014
Journal Name
International Journal Of Technical Research And Applications
SYNTHESIS, PHYSICO-CHEMICAL AND ANTIMICROBIAL PROPERTIES OF SOME METAL (II) -MIXED LIGAND COMPLEXES OF TRIDENTATE SCHIFF BASE DERIVES FROM Β-LACTAM ANTIBIOTIC {(CEPHALEXIN MONO HYDRATE)-4-CHLOROBENZALDEHYDE} AND SACCHARIN
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new Schiff base 4-chlorophenyl)methanimine (6R,7R)-3-methyl-8-oxo-7-(2-phenylpropanamido)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate= (HL)= C23H20 ClN3O4S) has been synthesized from β-lactam antibiotic (cephalexin mono hydrate(CephH)=(C16H19N3O5S.H2O) and 4-chlorobenzaldehyde . Figure(1) Metal mixed ligand complexes of the Schiff base were prepared from chloride salt of Fe(II),Co(II),Ni(II),Cu(II),Zn(II) and Cd (II), in 50% (v/v) ethanol –water medium (SacH ) .in aqueous ethanol(1:1) containing and Saccharin(C7H5NO3S) = sodium hydroxide. Several physical tools in particular; IR, CHN, 1H NMR, 13C NMR for ligand and melting point molar conductance, magnetic moment. and determination the percentage of the metal in the complexes by fl

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Publication Date
Thu Jan 23 2025
Journal Name
Journal Of Baghdad College Of Dentistry
In Vitro Evaluation of Shear Bond Strength of Sapphire Brackets after Dental Bleaching
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Background: The present study was conducted to evaluate the effects of different bleaching methods on the shear bond strength of orthodontic Sapphire brackets bonded to human premolars teeth using light cured composite resin and to determine the predominant site of bond failure. Materials and Methods: Thirty freshly extracted human premolars were selected and randomly divided into three groups (10 per group). These groups are: control (unbleached) group, hydrogen peroxide group (HP) 37.5% ; which is the in- office bleaching method group, carbamide peroxide group (CP) 16%; which is the at- home bleaching method group. After bleaching process was performed, all the teeth stored in distilled water in a sealed container at room temperature for

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Publication Date
Fri Jan 01 2016
Journal Name
Diyala Journal For Pure Sciences
Synthesis, Characterization and Biological Activity for Complexes VO(II), Mn(II), Co(II) and Ni(II) With New Multidentate Ligand [2-((E)-3-(2-hydroxyphenylimino)-1,5-dimethyl-2-phenyl-2,3-dihydro-1H-pyrazol-4- ylimino)acetic Acid][H2L] type (N2).
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In this work, the precursor [2-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-ylimino)acetic acid] was synthesised from 4-aminoantipyrine and glyoxylic acid, this precursor has been used in the synthesis of new multidentate ligand [2-((E)-3-(2-hydroxyphenylimino)-1,5-dimethyl-2-phenyl-2,3-dihydro-1H-pyrazol-4-ylimino)acetic acid][H2L] type (N2O2). The ligand was refluxed in ethanol with metal ions [VO(II), Mn(II), Co(II) and Ni(II)] salts to give complexes of general molecular formula:[M(H2L)2(X)(Y)].B, where: M=VO(II), X=0, Y=OSO3-2, B=2H2O; M=Mn(II),Co(II) ,X=Cl, Y=Cl, B=0; M=Ni(II), X=H2O, Y=Cl, B=Cl. These complexes were characterised by atomic absorpition(A.A), F.T-I.R., (U.V-Vis)spectroscopies (1H,13C NMR for ligand only), alon

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Publication Date
Sat Aug 15 2015
Journal Name
Chemistry And Materials Research
Synthesis and Characterization of 3, 5-Dimethyl-2-(4-nitrophenyl azo)-Phenol Complexes with Co (II) and Ni (II) and Study Its Effect on the Activity of Ach Enzyme (invitro)
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Publication Date
Sun Mar 04 2012
Journal Name
Baghdad Science Journal
Synthesis of New Mannich Bases from Indole Derivatives
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This work includes two steps of synthesis, the first one is the synthesis of indole which was prepared according to literature of the reaction of phenyl hydrazine with acetaldehyde in glacial acetic acid afforded phenyl hydrazone of acetaldehyde , this product was fused with zinc chloride to give the indole.Reaction of cyclohexanone with phenyl hydrazine using the same procedure for the preparing giving 1,2,3,4-Tetrahydrocarbazole.Second step involved synthesis of a series of (17) of mannich bases derivatives of indole and 1,2,3,4-Tetrahydrocarbazle. Mannich reaction involves the condensation of aldehyde usually formaldehyde with different secondary amine and with compound containing an activated hydrogen.The reaction illustrated by the fo

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