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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 Mar 28 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Dose Dependent Anti-inflammatory Effect of Ammi majus Alcoholic Extract in Rat: Chronic Study
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During treatment of inflammatory diseases, many conventional therapies (non-steroidal anti-inflammatory drugs) used to relief pain and inflammation. Chronic use of  the intended drugs is frequently associated with serious side effect, which may lead to discontinuation of treatment . The efficacy and dose- response effect of ammi majus extraxt  (2 , 4, 8 , 16, and 32 mg/rat) were assessed using  formalin to induce paw edema in rats as a model of chronic inflammation respectively. In this study,  42 rats were used and allocated into 7  groups each containing 6 rats, representing control (Distilled  water) , standard (piroxicam ) and test extract ( 2 , 4 , 8 , 16 and 32 mg/rat of Ammi majus alcoholic e

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Publication Date
Wed May 01 2024
Journal Name
Baghdad Science Journal
Synthesis, Spectroscopy and Biological Activity Study of Some New Complexes with Schiff Base Derived From Malonic Acid Dihydrazide with 2-pyridine Crboxaldehyde
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تم تحضير ثلاث معقدات جديدة Ni (II)و Cu (II) و Zn (II) باستخدام الليكند المحضر الجديد من تفاعل حامض مالونيك ثنائي هيدرازايد مع 2-بيريدين كربوكسالديهايد. حيث شخصت المعقدات لمحضرة وكذلك الليكند باستخدام تقنيات مختلفة مثل FT-IR و UV-Vis و Mass و 1H-NMR و 13C-NMR وتحليل العناصر CHN و تقدير محتوى  الكلور والموصلية المولارية والحساسية المغناطيسية والامتصاص الذري لتشخيص هذه المركبات. لكل معقد محضر جديد من النيكل والنحاس والزنك ، كشفت نتائج ا

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Publication Date
Wed Aug 30 2023
Journal Name
Al-kindy College Medical Journal
Maxillary Ameloblastic Fibroma: Two Case Reports of a Rare Tumor
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Ameloblastic fibroma is a rare benign tumor usually affects the first two decades of life. The neoplasm is more predominant in mandibular molar-premolar region and rarely affects the maxilla. In this report, we present a couple of Ameloblastic fibroma cases, affecting boys at their 1st decade. The lesions were presented as swellings of their maxilla, which is atypical location. Radiographic images showed well-defined radiolucency containing areas of radio-opacities and impacted teeth. Differential diagnosis was established as cystic/neoplastic conditions. The lesions were incised and histopathologically diagnosed as Ameloblastic fibroma, since they were composed of immature odontogenic mesenchymal and epithelial cells showing different c

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Publication Date
Wed Apr 02 2014
Journal Name
Journal Of Theoretical And Applied Information Technology
TUMOR BRAIN DETECTION THROUGH MR IMAGES: A REVIEW OF LITERATURE
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Today’s modern medical imaging research faces the challenge of detecting brain tumor through Magnetic Resonance Images (MRI). Normally, to produce images of soft tissue of human body, MRI images are used by experts. It is used for analysis of human organs to replace surgery. For brain tumor detection, image segmentation is required. For this purpose, the brain is partitioned into two distinct regions. This is considered to be one of the most important but difficult part of the process of detecting brain tumor. Hence, it is highly necessary that segmentation of the MRI images must be done accurately before asking the computer to do the exact diagnosis. Earlier, a variety of algorithms were developed for segmentation of MRI images by usin

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Publication Date
Tue Sep 01 2020
Journal Name
Al-khwarizmi Engineering Journal
Two-Stage Classification of Breast Tumor Biomarkers for Iraqi Women
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Objective: Breast cancer is regarded as a deadly disease in women causing lots of mortalities. Early diagnosis of breast cancer with appropriate tumor biomarkers may facilitate early treatment of the disease, thus reducing the mortality rate. The purpose of the current study is to improve early diagnosis of breast by proposing a two-stage classification of breast tumor biomarkers fora sample of Iraqi women.

Methods: In this study, a two-stage classification system is proposed and tested with four machine learning classifiers. In the first stage, breast features (demographic, blood and salivary-based attributes) are classified into normal or abnormal cases, while in the second stage the abnormal breast cases are

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Publication Date
Tue Mar 28 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Evaluation of Rosuvastatin Effect as Adjuvant Therapy to Methotrexate on Lipid Profile and the Possibility of its Cardioprotective Effect in Iraqi Patients with Active Rheumatoid Arthritis
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Rheumatoid arthritis (RA) is a common inflammatory disease that associated with increased morbidity and mortality due to accelerated atherosclerosis. Rosuvastatin is a unique hydroxy methyl glutaryl Co A (HMGCoA) reductase inhibitor that has anti inflammatory effects.

The aim of this study was to evaluate the effect of rosuvastatin as adjuvant therapy to methotrexate (MTX) on lipid profile and its possible cardioprotective effect in RA patients. A double blinded placebo controlled clinical trial with 8 weeks follow up periods at which 40 patients with active RA using MTX were randomized into 2 groups to receive either rosuvastatin 10mg or placebo as adjuvant therapy to MTX. In addition to twenty healthy subjects as control group.

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Publication Date
Sun Mar 17 2019
Journal Name
Baghdad Science Journal
A Study on the Accuracy of Prediction in Recommendation System Based on Similarity Measures
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Recommender Systems are tools to understand the huge amount of data available in the internet world. Collaborative filtering (CF) is one of the most knowledge discovery methods used positively in recommendation system. Memory collaborative filtering emphasizes on using facts about present users to predict new things for the target user. Similarity measures are the core operations in collaborative filtering and the prediction accuracy is mostly dependent on similarity calculations. In this study, a combination of weighted parameters and traditional similarity measures are conducted to calculate relationship among users over Movie Lens data set rating matrix. The advantages and disadvantages of each measure are spotted. From the study, a n

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Publication Date
Fri Feb 28 2014
Journal Name
Journal Of Natural Sciences Research
Synthesis, Characterization and Antimicrobial Investigations of (Ag, Cu, Ni, Co, Mn and Hg) Complexes with Schiff Base Derived From PVA and Erythro-Ascorbic Acid Derivative
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The aim of this work is the synthesis of new Schiff base derived from PVA and Erythro-ascorbic acid derivative (pentulosono-ɣ-lactone-2,3-enedianisoate) and its metal complexes of biological significance. All synthesized compounds were characterized by Thin layer chromatography (TLC) and FTIR spectra and aldehyde was also characterized by (U.V-Vis), 1HNMR, 13CNMR and mass spectra. The synthesized Schiff base & its metal complexes were screened for their in vitro antimicrobial activity against five pathogenic bacteria (Escherichia coli, Shigella dysentery,Klebsiellapneumonae,Staphylococcusaureus, Staphylococcus Albus) and two fungal (Aspergillus Niger,Yeast).The biological activity ofall complexes is higher than free Schiff base ligand andf

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Publication Date
Sun Dec 01 2013
Journal Name
Political Sciences Journal
Scientific Activities political systems
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نشاطات فرع النظم السياسية

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Publication Date
Mon Aug 01 2022
Journal Name
Baghdad Science Journal
Detection of Methamphetamine using Nanobentonite as a Novel Solid Phase Extraction Column Matrix Assisted with Gas Chromatography- Mass Spectroscopy
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          This study was done to evaluate a new technique to determine the presence of methamphetamine in the hair using nano bentonite-based adsorbent as the filler of extraction column. The state of the art of this study was based on the presence of silica in the nano bentonite that was assumed can interact with methamphetamine. The hair used was treated using methanol to extract the presence of methamphetamine, then it was continued by sonicating the hair sample. Qualitative analysis using Marquish reagent was performed to confirm the presence of methamphetamine in the isolate.The hair sample that has been taken in a different period confirmed that this current developing method can be used to analyzed methamphetamine. This m

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