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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 28 2023
Journal Name
Baghdad Science Journal
COMPARATIVE STUDY BETWEEN A NOVEL DETERMINISTIC TEST FOR MERSENNE PRIMES AND THE WELL-KNOWN PRIMALITY TESTS
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In this article, a new deterministic primality test for Mersenne primes is presented. It also includes a comparative study between well-known primality tests in order to identify the best test. Moreover, new modifications are suggested in order to eliminate pseudoprimes. The study covers random primes such as Mersenne primes and Proth primes. Finally, these tests are arranged from the best to the worst according to strength, speed, and effectiveness based on the results obtained through programs prepared and operated by Mathematica, and the results are presented through tables and graphs.

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Publication Date
Fri Dec 31 2021
Journal Name
Iraqi Journal Of Market Research And Consumer Protection
SYNTHESIS AND CHARACTERIZATION OF NEW β-LACTAM DERIVATVE FROM SULFADIAZINE DRUG BY MANY STEPS: SYNTHESIS AND CHARACTERIZATION OF NEW β-LACTAM DERIVATVE FROM SULFADIAZINE DRUG BY MANY STEPS
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This research involved synthesis of new β-Lactam derivative from Azo compound[4-amino-N-(pyrimidine-2-yl)-3-(pyrimidine-2-yldiazenyl) benzene sulfonamide] (S1) record previously by many steps. Starting conversion the free amino group in an azo comp. to chloro acetamide derivative(S2), then reacted it with urea to give the oxazole ring  derivative (S3) that which containing free amino group. The condensation reaction between the amino group and P-bromobenzaldehyde to produce Shiff base (B14). Finally staudinger's cyclo addition reaction go run between the Shiff base derivative (B14) and chloro acetyl chloride in the presence of tri ethyl amine (Et3N) as Base catalyst and dioxane a

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Publication Date
Fri Dec 14 2018
Journal Name
Iraqi National Journal Of Nursing Specialties
Evaluation of Quality of Primary Health Care Services at Primary Health Care Centers in Baghdad City: A Comparative Study
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Objective(s): To evaluate primary health care services at primary health care centers in Baghdad City and to compare between these primary health care centers relative to such quality. Methodology: A descriptive design, using the evaluation approach, is study to Evaluation of quality of primary care services at primary health care centers in Baghdad City. A multistage probability sample of (36) health care centers was selected. The sample consists of (12) model centers, (12) urban centers, and (12) rural centers.A constructedquestionnaire is composed of (23) items. It consisted of (5) parts that include inta

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Publication Date
Fri Nov 09 2018
Journal Name
Iraqi National Journal Of Nursing Specialties
Evaluation of Nurses' Practices toward the Control of Patients’ Complications at the Respiratory Care Unit in Baghdad Teaching Hospitals
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Objective(s): To evaluate nurses' practices who work in respiratory intensive care units to control the
complications of patients admitted at this unit and determine the relationship between nurses' sociodemographic
characteristics and their practices.
Methodology: A descriptive study was carried out at Respiratory Care Unit at Baghdad teaching hospitals that
started from February 22th, 2013 to August 30th, 2013. A purposive "non-probability" sample of (70) nurses who
work in Respiratory Care Unit was selected from Baghdad teaching hospitals. The data were collected through the
use of constructed questionnaire that consists of two parts; (l) Demographic data form that consists of 7items and
(2) nurses' practice form

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Publication Date
Sat Apr 01 2023
Journal Name
Baghdad Science Journal
Characterization of a novel pathway for xanthene degradation by the engineered strain Sphingobium yanoikuyae B1DR
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Polyaromatic hydrocarbons (PAHs) are a group of aromatic compounds that contain at least two rings. These compounds are found naturally in petroleum products and are considered the most prevalent pollutants in the environment. The lack of microorganism capable of degrading some PAHs led to their accumulation in the environment which usually causes major health problems as many of these compounds are known carcinogens. Xanthene is one of the small PAHs which has three rings. Many xanthene derivatives are useful dyes that are used for dyeing wood and cosmetic articles. However, several studies have illustrated that these compounds have toxic and carcinogenic effects. The first step of the bacterial degradation of xanthene is conducted by d

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Publication Date
Sat Apr 01 2023
Journal Name
Chemical Methodologies
A Novel Design for Gas Sensor of Zinc Oxide Nanostructure Prepared by Hydrothermal Annealing Technique
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Publication Date
Sun Aug 01 2021
Journal Name
Journal Of Physics: Conference Series
Evaluation and development of Shatt Al-Diwaniya and the diversion canal of Shatt Al-Diwaniya
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Abstract<p>Shatt Al-Diwaniya branches from Shatt Al-Hilla and extends for about 112 km until the Al-Rumaitha district within the study area located in Al-Diwaniya Governorate, Iraq. It is considered the main source for providing drinking water and supplying irrigation projects to the cities Al-Diwaniya and Al-Rumaitha. The study aims to evaluate, study, and develop Shatt Al-Diwaniya, as well as the new lined canal branching from Shatt Al-Diwaniya which. It is called Shatt Al-Diwaniya Diversion Canal. Field measurements of the discharge and water level were monitored, six sets for Shatt Al-Diwaniya and three sets for Diversion Canal. A one-dimensional model was developed by using HEC-RAS 5.0.7 so</p> ... Show More
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Publication Date
Sun Jul 25 2021
Journal Name
Natural Resources Research
Effect of Water Flooding on Oil Reservoir Permeability: Saturation Index Prediction Model for Giant Oil Reservoirs, Southern Iraq
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Publication Date
Mon Jan 01 2024
Journal Name
Iraqi Journal Of Hematology
Provisional diagnosis of clinically significant hemoglobinopathies and decision on suitability for marriage as part of the premarital screening program in Iraq: Iraqi Society of Hematology Guidelines
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Publication Date
Thu Nov 01 2018
Journal Name
Journal Of Economics And Administrative Sciences
Marketing decisions as an intermediary variable of the nature of the relationship between Environmental Turbulence and marketing effectiveness exploratory study of Carrefour branches in Erbil Governorate
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The organizations, represented by its Management, are working hard in various ways to identify the environmental disturbances that occur in their environment and to investigate and follow up the movement of these disturbances and to respond to them through the decisions they make in an attempt to keep pace with the work and sustainability of their activities, including those decisions, marketing decisions taken by the environmental disturbulence in the market of the organization, the inability of these organizations to read the indicators of these disturbulence correctly displays their marketing effectiveness to vibration and decline in the negative.The current research is based on a fundamental problem that envi

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