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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 Oct 01 2022
Journal Name
The Egyptian Journal Of Hospital Medicine
Evaluation of Some Pro-Inflammatory Cytokines Level in Sample of Iraqi Patients with Hyperthyroidism
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Background: Hyperthyroidism is a serious public concern, due the continuous increase in its prevalence and its impact on the mortality rates. Autoimmune hyperthyroidism is seen as a thyroid gland problem. Pro-inflammatory cytokines are crucial for the growth and development of hyperthyroidism, it was shown that the level of several pro-inflammatory cytokines were higher in the hyperthyroidism patients. Objective: This work was aimed to assessment the concentration of certain cytokine in hyperthyroid patients. Materials and Methods: Sixty hyperthyroidism patients and 30 healthy individuals with age range from (30-65) years old were enrolled in this study through their presence at the National Center for Diabetes Treatment and Research in Bag

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Publication Date
Mon May 01 2023
Journal Name
Wiadomości Lekarskie Medical Advances
EVALUATION OF VEST-OVER-PANT TECHNIQUE IN THE TREATMENT OF POST-HYPOSPADIAS URETHROCUTANEOUS FISTULA
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The aim: In this study, we present and evaluate the vest-over-pants technique as a simple way to correct urethrocutaneous fistulas after hypospadias. Materials and methods: Between October 2018 and June 2020, twenty male patients aged 5 to 20 years came to us with post hypospadias repair fistula, these patients underwent vest-over-pant repair of their fistula. The size of fistula was ranging between 2.5-5 mm. The distribution of fistula was coronal (3 patients), distal penile (9 patients), midshaft (2 patients) and proximal penile (6 patients). In 14 patients there were single fistula and 6 patients had more than one fistula. Eleven of patients were exposed to a previous failed fistula repair procedure. Results: Six months after the operati

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Publication Date
Fri Jan 01 2021
Journal Name
Wiadomości Lekarskie
EVALUATION THE EFFECT OF PRODIGIOSIN ON ALGD EXPRESSION IN CLINICAL ISOLATES OF PSEUDOMONAS AERUGINOSA
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The aim of this study is to investigate the role of prodigiosin on P. aeruginosa' s biofilm genes involved in the pathogenicity and persistency of the bacteria; Materials and methods: Gram negative bacterial isolates were taken from burn and wounds specimen obtained from some of Baghdad hospitals. Forty six isolates were identified as Pseudomonas aeruginosa and four isolates as Serratia marcescens by using biochemical tests and VITEK 2 compact system. Susceptibility test was performed for all P. aeruginosa isolates, the results showed that 100% were resistant to Amikacin and 98% were sensitive to Meropenem. Resistant isolates were tested for biofilm formation; the strong and moderate isolates (17) were detected by PCR for AlgD gene

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Publication Date
Sun Jan 01 2023
Journal Name
Journal Of Engineering
Evaluation of the Current Status of the Cost Control Processes in Iraqi Construction Projects
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One of the most important problems of Iraqi construction projects is the cost variances, so it is important to identify the problems and shortcomings that cause poor cost control. Through the utilization of questionnaires, the study evaluated how project costs were managed and reported. The questionnaire was distributed to 180 professionals working in the Iraqi construction sector, with a response rate of 91%. The results showed that a high percentage of projects are implemented with a difference between real and estimated costs, and the process of documenting cost data needs to be more secure. On the other hand, there is a weakness in providing the necessary work structure information to monitor costs and a lack of proc

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Publication Date
Tue Jun 30 2009
Journal Name
Al-kindy College Medical Journal
Evaluation of Serum Interleukin-6 Levels in Correlation to the Severity of Acute Appendicitis
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Background: Acute appendicitis is a common surgical
problem that is associated with an acute-phase reaction.
Previous studies have shown that cytokines and acutephase proteins are activated and may serve as indicators for
appendicitis.
Objective: The aim of this study was to evaluate of serum
levels of interleukin-6 (IL-6) in correlation to the severity
to acute appendicitis.
Methods: This is a prospective study from December 2008
to March 2009 of patients who had appendectomy in
Department of Surgery, Al-Kindy Teaching Hospital -
Baghdad/Iraq. Serum for estimating levels of interleukin-6
(IL-6) was taken pre-operatively. Depending on the
macroscopic evidence during the operation and the
histopathol

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Publication Date
Mon Jan 01 2024
Journal Name
Heliyon
Synthesis and Characterization of Some Metal Ions Complexes with Mixed Ligand of Azo Dye and Metformin and Evaluation of its Effectiveness on the Growth of Some Pathogenic Bacteria Clinically Isolated and Study of its Toxicity on Normal and Cancerous Hepatocytes
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Publication Date
Sun Sep 01 2024
Journal Name
Heliyon
Synthesis and characterization of some Metal ions complexes with mixed ligand of azo dye and Metformin and evaluation of its effectiveness on the growth of some pathogenic bacteria clinically isolated and study of its Toxicity on normal and cancerous Hepatocytes
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Publication Date
Sun Sep 01 2024
Journal Name
Heliyon
Synthesis and characterization of some Metal ions complexes with mixed ligand of azo dye and Metformin and evaluation of its effectiveness on the growth of some pathogenic bacteria clinically isolated and study of its Toxicity on normal and cancerous Hepatocytes
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Four metal compounds mixed ligand of azo dye ligand (L) and metformin.(Met) were produced at aquatic ethanol for (1:1:1) (M:L:Met). The prepared compounds were identified by utilizing atomic absorption flame, FT.IR and UV–Vis spectrum manners as well as conductivity mensuration. These compounds was assayed of the gained datum the octahedral geometry was proposed into whole prepared complexes.Also in this research was studied represented examining the antibacterial and antifungal impact of the azo dye ligand (L), metformin.(Met) and (Co,Ni, Cu and Cd complexes) on four types of pathogenic, clinically isolated bacteria that are resistant to antibiotic, like Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Klebsiella pneu

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Publication Date
Mon Apr 01 2024
Journal Name
Medical Journal Of Babylon
Clinical Evaluation and Comparison between Effects of Rituximab and Prednisolone with Imuran to Neutrophils and Platelet Counts in Pemphigus Vulgaris Patients
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Background: Pemphigus vulgaris (PV) is an autoimmune vesiculobullous mucocutaneous disease with life-threatening consequences. Rituximab (RTX) has recently emerged as an effective treatment for PV. Objectives: This study aims to determine changes in neutrophil and platelet counts for PV patients treated with RTX or corticosteroids combined with Imuran (azathioprine). Materials and Methods: The present cross-sectional study was conducted in the Department of Dermatology at Baghdad Teaching Hospital, Baghdad, Iraq. Thirty PV patients received two types of treatment: 15 patients were administered RTX and 15 patients took corticosteroids with Imuran (azathioprine). Neutrophil and platelet counts were detected at the hospital laboratory. Results

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Publication Date
Fri Dec 01 2023
Journal Name
Al-nahrain Journal Of Science
The Efficiency of Titanium-Graphite Electrode Cells in the Presence of Ionic Liquids and Deep Eutectic Solvents as Electrolytes
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Prior to the start of production, several factors must be considered, including the price, effectiveness, and environmental friendliness of batteries. Ionic liquids and deep eutectic solvents have shown significant success when employed as electrolytes with Titanium-graphite cells, especially when combined with additives that enhance their conductivity by reducing the high viscosity of these liquids. Evaluating the discharge voltage of the AlCl3-chloroacetamide IL with DCM as an additive revealed a voltage of 1.16V and an internal resistance of 11 Ohm. These electrochemical cells exhibited an intriguing response. Otherwise, when utilizing CaCl2.2H2O:

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