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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
Sun Jan 01 2023
Journal Name
Materials Today: Proceedings
Preparation, characterization and preliminary cytotoxic evaluation of 6-mercaptopurine-coated biotinylated carbon dots nanoparticles as a drug delivery system
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Publication Date
Sun Jan 01 2023
Journal Name
Materials Today: Proceedings
Preparation, characterization and preliminary cytotoxic evaluation of 6-mercaptopurine-coated biotinylated carbon dots nanoparticles as a drug delivery system
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Publication Date
Mon Aug 01 2022
Journal Name
Baghdad Science Journal
Evaluation of Turkish Delight Prepared With Pigments And Essential Oils Extracted From Clementine (Citrus Clementine) Peels As Natural Antioxidants
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This experiment presented essential oils by GC/MS, pigment content, and their antioxidant activities as well as sensory evaluation of delight samples. Limonene (66.88%) was the most prevalent yield. The peels of clementine had DPPH and ABT Scavenging activity. All levels of pigment extract had better scores for all sensory values and recorded acceptable scores in terms of appearance, color, aroma, and overall acceptability compared to control delight. Besides, delight samples containing 15 mg astaxanthin pigment extract showed maximum sensory scores compared to other samples and control delight. On the other hand, the product was less acceptable to the panelists compared to control in the case of the addition of 3.75 mg astaxanthin pigme

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Publication Date
Fri Nov 24 2023
Journal Name
Iraqi Journal Of Science
Cloning of Copper resistance gene (copA) that Presence in Novel Genomic Island of Acinetobacter baumannii A92
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This study was aimed to detect weather copA gene(copper resistance gene ) presence in A.baumannii A92 genome(AbaR genomic islands). The full genomic sequence of A.baumannii A92 not published in NCBI genome similarity was detected between two strains so the sequence of A.baumanniiIS-116(Genebank-AMGF0100000.1 ) was used to design the primers that were used for amplify of copA gene of A.baumannii A92.
Two primers contain two sites for restriction enzymes (KpnI,XohI) and PWSK29 vector were used in the cloning, double digestion has been performed for vector and gene. Then the re-ligation was completed to form recombinant molecule,after that, transformation have been performed for the recombinant molecule by using chemical competent E.coli

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Publication Date
Sun Jan 01 2017
Journal Name
Journal Of Engineering
Evaluation of Textile Filter in Field Drains
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The role of drain in agricultural lands is to remove excess surface and subsurface water to create a good environment for root growth and to increase crops yield. The main objective of this research was to evaluate the performance of closed drains when using textile filter instead of crushed gravel filter. The research has been executed in the laboratory using a sand tank model and by using two types of the soil. One of soils was light soil (sandy soil) and the other heavy soil (loamy soil). The tests were classified into four cases; each case was supplied discharge during 10 days. The results showed that the amount of out flow when using graded crushed gravel filter is greater than the amount of out flow in case of usin

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Publication Date
Tue Nov 22 2016
Journal Name
Der Pharma Chemica
Evaluation of Commercial Antacid Tablets in Iraq
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Antacids are commonly used drugs which are considered inert and free of pharmacological effect by many patients and physicians. They are weak bases that neutralize the gastric acid and relief pain. These weak bases dissociate to neutralize gastric acid and form neutral salts. The ultimate goal of antacid therapy is to reduce the concentration and a total load of acid in gastric juice to a pH 4 - 5. This in vitro study was promised to study the acid neutralizing capacity (ANC) of six commonly available antacids tablets in the Iraqi market by using back titration method. The highest ANC values were for Rennie (17.131± 0.083 and 16.926± 0.052 mEq) in two different hydrochloric acid (HCl) concentrations 1N and 0.5 N, respectively. The static

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Publication Date
Thu Nov 02 2017
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
A Bacterial Evaluation Of Tonsillitis In Baghdad
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A sample  of  168 tonsillitic  subjects  (93  males and  75 females), livin g in Baghdad was evaluated  microbiologically.   The patients  had an age  range  of  3-35  years.          Four  bacterial   species  were   isolated  and identified.    They             were              P-haemolyt ic Streptococcus    ,(39.3%) Staphylococcus                  

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Publication Date
Thu Apr 20 2023
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
Evaluation of Asprosin Hormone in Hypothyroidism Patients
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Asprosin was a novel adipokine that was released by white adipose tissue. It was activated by fasting and attracted to the liver, which allowed the liver to rapidly release glucose into the bloodstream. White adipose tissue was the source of asprosin. When people go on a fast, their blood sugar levels drop, which causes levels of the hormone asprosin to rise. It does this by binding to a G-protein-coupled receptor in the liver known as OR4M1, which in turn activates a cascade that involves the G -protein-cAMP-PKA pathway. Because of this, the glucose that is stored in the liver is released.  We anticipate that by investigating the changes that occur in asprosin levels in hypothyroidism patients, we will be able to make a significant

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Publication Date
Sun Dec 30 2012
Journal Name
Al-kindy College Medical Journal
Evaluation of Medication Errors in Hospitalized Patients
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Objectives: Many medication errors occur in the hospital, and these can endanger patients. The purpose of this study was to evaluate the incidence of medication errors in hospitalized patients, and to categorize the most frequent types of errors, and to asses the possible measures that may prevent the occurrence of such errors.
Methods: A prospective, exploratory, and evaluative study, using direct observation method to detect medication errors in adult hospitalized patients in medical and surgical units in Baquba Teaching Hospital- Diyala-Iraq.. The files of 299 patients had been reviewed from July 2009 to September 2009, including medication orders and treatment sheets to detect existing errors. The detected errors were recorded and

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Publication Date
Sat Dec 30 2023
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Multiphase Flow Behavior Prediction and Optimal Correlation Selection for Vertical Lift Performance in Faihaa Oil Field, Iraq
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In the petroleum industry, multiphase flow dynamics within the tubing string have gained significant attention due to associated challenges. Accurately predicting pressure drops and wellbore pressures is crucial for the effective modeling of vertical lift performance (VLP). This study focuses on predicting the multiphase flow behavior in four wells located in the Faihaa oil field in southern Iraq, utilizing PIPESIM software. The process of selecting the most appropriate multiphase correlation was performed by utilizing production test data to construct a comprehensive survey data catalog. Subsequently, the results were compared with the correlations available within the PIPESIM software. The outcomes reveal that the Hagedorn and Brown (H

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