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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 Mar 09 2017
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
Synthesis and Characterization of Some New Complexes With New Schiff Base Type (N2O2) Derived From Glyoxylic Acid and Ethylenediamine
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New tetradentate Schiff base [H2L] namely [2,2׳ -(ethane-1,2- diylbis (azan-1-ylylidene) diacetic acid)] was prepared from condensation of ethylenediamine with  glyoxylic acid  in ethanol as a solvent in presence of drops of 48% HBr .The structure of ligand (H2L) was characterized by,F-IR, U.V-Vis.,1H-,13C-NMR, pectrophotometer,melting point and elemental microanalysis C.H.N.  Metal complexes of the ligand (H2L) in general Molecular formula [M(L)(H2O)2], where M=  Co(II), Ni(II), Cu(II), Mn(II) and Hg(II); L=(C6H8N2O4) were synthesized were characterized by, Atomic absorption, F-IR, U.V-Vis. spectra, molar conductivity and magnetic susceptibility.It was found that all the complexes showed octahedral geometries.And

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Publication Date
Tue Jan 03 2023
Journal Name
The Egyptian Journal Of Hospital Medicine
High Tumor Levels of Ki-67, VEGF and Endostatin Are Associated with Progression of Breast Cancer in Iraqi Women
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Background: Breast cancer (BC) is the most widespread cancer among women worldwide. Its incidence and mortality rates have risen in the previous three decades as a result of changes in risk factor profiles, improved cancer registry, and cancer detection. Objective: The study's goals were to establish if Ki-67 could be used as a potential marker in serum of cancer disease patients as well as their interaction with vascular endothelial growth factor (VEGF) and ES in various stages of breast cancer to assess their function in the progression of BC. Materials and Methods: The levels of Ki-67, VEGF and endostatin (ES) in serum were assessed by commercial enzyme linked immunosorbent assay (ELISA) kits in 60 women diagnosed with breast cancer

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Publication Date
Sun Jan 01 2023
Journal Name
The Egyptian Journal Of Hospital Medicine
High Tumor Levels of Ki-67, VEGF and Endostatin Are Associated with Progression of Breast Cancer in Iraqi Women
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Publication Date
Mon Dec 18 2017
Journal Name
Al-khwarizmi Engineering Journal
Prediction of Surface Roughness and Material Removal Rate in Electrochemical Machining Using Taguchi Method
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Electrochemical machining is one of the widely used non-conventional machining processes to machine complex and difficult shapes for electrically conducting materials, such as super alloys, Ti-alloys, alloy steel, tool steel and stainless steel.  Use of optimal ECM process conditions can significantly reduce the ECM operating, tooling, and maintenance cost and can produce components with higher accuracy. This paper studies the effect of process parameters on surface roughness (Ra) and material removal rate (MRR), and the optimization of process conditions in ECM. Experiments were conducted based on Taguchi’s L9 orthogonal array (OA) with three process parameters viz. current, electrolyte concentration, and inter-electrode gap. Sig

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Publication Date
Sun Sep 06 2009
Journal Name
Baghdad Science Journal
Cultivation of Entamoeba histolytica in vitro and diagnose the bacterial growths in culture media
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The parasite was isolated from a stool sample, cultivated and maintained in vitro using Locke-egg medium (LEM) and Liver infusion agar medium (LIAM) . The culture was maintained for up to 21 months, and the best time to maintain the parasite was every 48 hours, although the growth in the culture media continued for 13 days without a maintenance. Additionally, no cyst formation was observed during cultivation of parasite in the two culture media. Although, was observe young cyst formed in LEM media were deletion of maintained. The diagnosis of bacteria growth in the culture media, bacterial content (Escherichia coli) was an dominance and essential requirement for a successful cultivation of Entamoeba histolytica in the two culture media.

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Publication Date
Sat Nov 28 2020
Journal Name
Iraqi Journal Of Science
Evaluation of the Biological Activity of Nickel Oxide Nanoparticles as Antibacterial and Anticancer Agents
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In the present study, nickel oxide nanoparticles (NiO NPs) were evaluated as an antibacterial and anticancer agent. The nanoparticles of nikel oxide were synthesized using aloe vera leaves extract and characterized with AFM (showing an average diameter of 45.11 nm), XRD and FE-SEM analyses. Three different concentrations (125, 250 and 500 µg/ml) were prepared from the synthesized NiO NPs and investigated for their potential antibacterial activity against both Enterococcus faecalis (Gram-positive bacteria) and Acinobacter baumannii (Gram-negative bacteria). While cytotoxicity and apoptotic activity were measured on both MCF-7 and AMJ13 cancer cell lines by  MTT and caspase-9 luminescence assays. The results showe

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Publication Date
Mon Apr 01 2024
Journal Name
Indonesian Journal Of Chemistry
Preparation, Characterization, and Biological Activity of La(III), Nd(III), Er(III), Gd(III), and Dy(III) Complexes with Schiff Base Resulted from Reaction of 4-Antipyrinecarboxaldehyde and 2-Aminobenzothiazole
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The research includes the preparation of several complexes of the internal transition elements lanthanide (Ln = La, Nd, Er, Gd, and Dy) containing the 4f shell, with Schiff bases resulting from condensation reactions between 4-antipyrinecarboxaldehyde and 2-aminobenzothiazoles. Schiff's base was identified using FTIR spectra, UV-vis spectroscopy, elemental microanalysis CHNSO, nuclear magnetic resonance, mass spectrometry, and TGA thermal analysis. The complexes were studied and identified with elemental microanalysis CHNSO, FTIR spectroscopy, UV-vis spectroscopy, TGA thermal analysis, conductivity measurement, and magnetic sensitivity. The result showed that these complexes were classified as homogeneous bidentate complexes with th

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Publication Date
Sun Sep 07 2008
Journal Name
Baghdad Science Journal
Corrosion Inhibition of Al-Si-Cu Alloy in the Basic Media by UsingSix Inhibitors at Four Temperatures
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The research involved attempt to inhibit the corrosion of Al-Si-Cu alloy in 2.5x10-3 mol.dm-3 NaOH solution (pH=11.4) by addition of six different inhibitors with three concentrations (1x10-3, 1x10-2, and 0.1 mol.dm-3). These inhibitors include three organic materials (sodium acetate, sodium benzoate, and sodium oxalate) and three inorganic materials (sodium chromate, disodium phosphate, and sodium sulphate). The data that concerning polarization behaviour are calculates which include the corrosion potential (Ecorr) and current density (icorr), cathodic and anodic Tafel slopes (bc & ba), and polarization resistance (Rp). Protection efficiency (P%) and activation energy (Ea) values were calculated for inhibition by the six inhibitors. The

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Publication Date
Thu Jun 30 2022
Journal Name
International Journal Of Drug Delivery Technology
Physiological and Immunological Assessment in Infertile Women Undergoing In-vitro Fertilization
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All the available reports on the issue of infertility confirmed the increase in this population problem worldwide. Although the accurate estimate of the number of infertile people is due to several reasons, including the discrepancy in the true definition of infertility (whether it extends for one, two or five years of failed pregnancy attempts), as well as the great discrepancy in the size of the selected population groups (large population sample size versus epidemiological studies) and defining the category that diagnosed included (individuals, women, or couples). The goal of today’s IVF program is to obtain high-quality embryos with high efficiency in development, which leads to an increase in live birth rates.

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Publication Date
Sun Sep 01 2013
Journal Name
Journal Of Baghdad College Of Dentistry
Gingival and Alveolar Ridge Tumor - Like Overgrowth Lesions
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Background: Tumor-like overgrowth lesions of the oral mucosa are pathological growths that project above the normal contour of the oral surface. A practical classification can be made according to the site of origin, the etiology and the histological appearance. The aim of this article is to evaluate and analyze patients with gingival and alveolar ridge tumor-like overgrowth lesions in terms of surgical treatment, diagnosis and outcome. Materials and Methods: Patients complaining of these lesions were treated by surgical excision under local or general anesthesia; the excised lesions were submitted for histopathological examination, during the follow up period the patients were examined for complications and recurrence. Results: Pyogenic gr

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