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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
Tue Feb 01 2022
Journal Name
Macromolecular Symposia
Synthesis of 5‐Fluorouracil–Naproxen Conjugates as a Mutual Prodrug for Targeting Cancer Tissues
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Abstract<p>A new 5‐fluorouracil–naproxen conjugate is synthesized as a mutual prodrug for targeting cancer tissues. The structure of the target compound and their intermediate are characterized by their melting point, IR, <sup>1</sup>H NMR, <sup>13</sup>C NMR, and elemental microanalysis. The cytotoxic activity is preliminarily evaluated using nonsmall lung cancer CRL‐2049, human breast cancer CAL‐51, and one type of normal cell line; rat embryo fibroblast cell line. The synthesized compound shows a good cytotoxic effect at the cancer cell and no significant effect at rat embryo fibroblast cell line.</p>
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Publication Date
Tue Aug 05 2014
Journal Name
International Journal Of Pharmacy And Pharmaceutical Sciences
FORMULATION AND EVALUATION OF FLOATING ORAL IN-SITU GEL OF METRONIDAZOLE
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Publication Date
Fri Sep 15 2023
Journal Name
Journal Of Baghdad College Of Dentistry
Evaluation of alpha amylase and peroxidase in saliva of pregnant women
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Background: Pregnancy is a natural physiological state that involves several biochemical modifications. Saliva is consisted of many types of proteins such as salivary alpha amylase and salivary peroxidase that might be affected by pregnancy. The former enzyme is considered one of the most prevalent proteins that is released by highly differentiated epithelial acinar cells and has been shown to have enzymatic activities while the latter has been approved that it  has a significant role in oral health. The purpose of this study was to the evaluate the salivary levels of alpha-amylase and peroxidase in pregnant and non-pregnant women. Materials and Methods: Sixty pregnant women were grouped according to the pregnancy trimesters. The first

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Publication Date
Sat Nov 28 2020
Journal Name
Iraqi Journal Of Science
Electrochemical Deposition of Hydroxyapatite Co-Substituted By Sr/Mg Coating on Ti-6Al-4V ELI Dental Alloy Post-MAO as Anti-Corrosion
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This work involved the co-substitution of the two bioactive ions of strontium and magnesium into the hydroxyapatite (HA) coating which was then electrochemically deposited on Ti-6Al-4V ELI dental alloy (Gr.23) before and after treatment by Micro Arc Oxidation (MAO). The deposited layers were characterized by scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). The adhesion strength of the coating layer was estimated by using pull-off adhesion test. The adhesion strength of Sr/Mg-HA on the Ti-6Al-4V ELI dental alloy after MAO treatment was 1.79 MPa, which was higher than that before MAO treatment (1.62 MPa). The corrosion behavior of th

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Publication Date
Sat Jun 18 2022
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Some Pro and Anti-Inflammatory Cytokines in Children with Tonsillitis and their Correlations with Vitamin D Deficiency
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Inflammation of the tonsils could be described as acute tonsillitis, mainly due to infection. Recurrent tonsillitis could be defined as 3-7 episodes during the first 3 years of age. Vitamin D, which is a neuro-hormone with pleiotropic biological activities may modulate the immune response by alleviation, and stimulation of Th1 and Th2 cell proliferation, respectively, that influence the stimulation, synthesis, and secretion of both pro and anti-inflammatory cytokines. In this study we aimed to shed light on the levels of vitamin D in children with different episodes of tonsillitis in association with levels of interleukins (TNFα, IL-2, IL-4, IL-10). Blood samples were collected from 48 participants in 3 groups: control, acute tonsilliti

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Publication Date
Wed Mar 10 2021
Journal Name
Baghdad Science Journal
studies of human interferon a B and Y activities on diffrent cell
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Human interferon as is the case in all kinds of interferon has complex effects but all share their impact on preventing the proliferation of viruses and preventing or reducing human Alantervjørn conversion occurs if the cell is in preventing the growth of the virus when interferon Balnmstqubl connects

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Publication Date
Sun Jan 21 2018
Journal Name
Drug Invention Today
Preparation and evaluation of lornoxicam in situ gelling liquid suppository
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Publication Date
Sun Jul 17 2022
Journal Name
Pharmacy Education
Students' experience and evaluation of community pharmacy internship in Iraq
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Background: Pharmacy internship programmes are driven by most developed countries to outweigh the ongoing growth in the pharmacy career which encourages pharmacists to play a significant role as healthcare providers.    Objectives: This study examines pharmacy students' perception, satisfaction, challenges, and limitations with the internship curriculum.    Method: A cross-sectional study was conducted using an online survey with different elements to examine students' perceptions of various aspects.    Result: Most students reported a positive impression regarding their internships, however, they were less satisfied with the allowance for filling prescriptions and compounding also, the college's follow-up was inadequate. F

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Publication Date
Fri Jan 26 2024
Journal Name
Iraqi Journal Of Science
Simulation and Evaluation of Soliton Signal Effects In Fiber Optics
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A soliton is a solitary wave whose amplitude, shape, and velocity are conserved after a collision with another soliton. Solitons, in general, manifest themselves in a large variety of wave/particle systems in nature: practically in any system that possesses both dispersion (in time or space) and nonlinearity. Solitons have been identified in optics, plasmas, fluids, condensed matter, particle physics, and astrophysics. Yet over the past decade, the forefront of soliton research has shifted to neuroscience. The Soliton model in optical fiber is a recently developed model that attempts to explain how signals are propagated within optical fiber without dispersion. In this research, it proposes that the signals travel along the Single Mode O

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Publication Date
Sun Jan 01 2023
Journal Name
Journal Of Advanced Pharmaceutical Technology &amp; Research
Use of factorial design in formulation and evaluation of intrarectal in situ gel of sumatriptan
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