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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 12 2024
Journal Name
Biomolecules
Limonene Exerts Anti-Inflammatory Effect on LPS-Induced Jejunal Injury in Mice by Inhibiting NF-κB/AP-1 Pathway
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The human gastrointestinal system is a complex ecosystem crucial for well-being. During sepsis-induced gut injury, the integrity of the intestinal barrier can be compromised. Lipopolysaccharide (LPS), an endotoxin from Gram-negative bacteria, disrupts the intestinal barrier, contributing to inflammation and various dysfunctions. The current study explores the protective effects of limonene, a natural compound with diverse biological properties, against LPS-induced jejunal injury in mice. Oral administration of limonene at dosages of 100 and 200 mg/kg was used in the LPS mouse model. The Murine Sepsis Score (MSS) was utilized to evaluate the severity of sepsis, while serum levels of urea and creatinine served as indicators of renal f

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Publication Date
Wed Jan 01 2025
Journal Name
Journal Of Discrete Mathematical Sciences And Cryptography
A novel cryptosystem using integer power
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Various methods are utilized providing complexity for cryptosystem with the aim to increase the security and avoiding hacker attack. Hybrid cryptosystem is one of these cryptosystems which is used two types of cryptosystems and has many applications in data transmitted. This research, proposed a novel method that used power exponent instead of using the prime number directly and also providing complexity of asymmetric cryptosystems. This method has been applied theoretically in two public systems RSA and EL-Gamal. Power RSA and Power EL-Gamal are modified asymmetric cryptosystems, in which the power number is kept by the sender and the receiver. Moreover, we use group theory to prove that these cryptosystems work properly. Our exten

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Publication Date
Sun Feb 25 2024
Journal Name
Baghdad Science Journal
SBOA: A Novel Heuristic Optimization Algorithm
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A new human-based heuristic optimization method, named the Snooker-Based Optimization Algorithm (SBOA), is introduced in this study. The inspiration for this method is drawn from the traits of sales elites—those qualities every salesperson aspires to possess. Typically, salespersons strive to enhance their skills through autonomous learning or by seeking guidance from others. Furthermore, they engage in regular communication with customers to gain approval for their products or services. Building upon this concept, SBOA aims to find the optimal solution within a given search space, traversing all positions to obtain all possible values. To assesses the feasibility and effectiveness of SBOA in comparison to other algorithms, we conducte

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Publication Date
Sat Dec 31 2022
Journal Name
Iraqi Journal Of Market Research And Consumer Protection
SYNTHESIS AND CHARACTERIZATION OF NEW DEMULSIFIER FROM NATURAL AND SYNTHETIC POLYMER: SYNTHESIS AND CHARACTERIZATION OF NEW DEMULSIFIER FROM NATURAL AND SYNTHETIC POLYMER
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ABSTRACT

This research included the preparation and characterization of new demulsifies from natural and synthetic polymers of chitosan and polyvinyl alcohol that are environmentally friendly and at the same time have high efficacy comparable to emulsifiers. imported foreign. The prepared compounds were examined using infrared spectroscopy and nuclear magnetic resonance spectroscopy, and all the spectral signals of the polymers were in good agreement with the chemical composition of the polymers. And the melting and decomposition that occur on polymers at high temperatures. The effect of the length and type of side chain in the compositions of polymers on the process of water separation of oil emulsions w

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Publication Date
Tue Dec 11 2018
Journal Name
Iraqi National Journal Of Nursing Specialties
Evaluation of Nursing staff Performance in Cardiac Care Units at Teaching and Non Teaching Hospitals in Kirkuk City: A Comparative Study
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Objective: The descriptive study was used to evaluate nursing staff performance in cardiac care units at teaching
and non teaching hospitals in kirkuk city: A comparative study.
Methodology: A descriptive study was used to evaluate nursing staff performance in cardiac care units. The study
was conducted from December 29th
, 2013 up to the 27th of Apr. 2014. A non-probability (purposive) sample of
(44) nurses who work in cardiac care unit at Azady teaching Hospital and Kirkuk general Hospital was evaluated by
a questionnaire which consisted of two parts; the first part is concerned with the demographic characteristics of
the nurses and the second part concerned Observation check list for evaluation nursing staff Perfo

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Publication Date
Thu Mar 05 2026
Journal Name
Sciences Journal Of Physical Education
تأثير التدريب بطريقة ( super site ) على بعض المؤشرات الفسيولوجية ومهارة الضربة الساحقة للاعبي الريشة الطائرة فئة الشباب
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هدف البحث الى اعداد تمرينات super site)) للاعبي الريشة الطائرة فئة الشباب ، ومعرفة تأثير التمرينات على بعض المؤشرات الفسيولوجية ومهارة الضربة الساحقة لدى لاعبي الريشة الطائرة فئة الشباب ، وتم تحديد مجتمع البحث من لاعبي الريشة الطائرة فئة الشباب لنادي الارمني وتم اختيار عينة البحث بالطريقة العمدية (8) لاعبين بالريشة الطائرة من النادي الارمني واستخدمت الباحثتان المنهج التجريبي ذو الاختبار القبلي والبعدي .ويهدف ال

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Publication Date
Tue May 16 2023
Journal Name
Political Sciences Journal
Institutional Reality Construction: Principles of its Construction and Functions of Language in its Production; Diplomacy as a Model
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This study aims to answer a significant problem of social sciences and philosophy: How do we construct an institutional reality such as diplomacy with an objective recognizable existence? The study assumes that the ability to build institutional reality is based on our biological capacity, as it takes different forms in all the institutions we construct. The study takes the theory of the American philosopher John Searle as an approach to examining the assumption. The study sums up important findings; cultures, although they share the biological capacity on which they produce institutional realities, differ in the form of the value standards on which the institutional realities are based. The study recommends the need of Arab social resea

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Publication Date
Tue Mar 31 2020
Journal Name
College Of Islamic Sciences
The Origin of Creation in Khattab (The Beginning of Creation) by Imam Ali (as) and Genesis (Comparative Study)
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The research aims to answer the questions that revolve in the mind of mankind about how to create creation, how it existed prior to creation, who created existence, and the characteristics of that presence. The researcher also wanted to show that the culture of Imam Ali (peace be upon him) In the book of Adam, peace be upon him, God has punished Adam (peace be upon him) for not having sinned. Because his wife is the one who fed him the fruit of the tree, and this is contrary to what was stated in the sermon of Imam (peace be upon him) who Z Adam (peace be upon him) is the one who trusted Satan and Gwighth.

We note that the approach of the rhetoric has pointed to the creation of angels and did not refer to

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Publication Date
Tue Jan 14 2020
Journal Name
College Of Islamic Sciences
The Origin of Creation in Khattab (The Beginning of Creation) by Imam Ali (as) and Genesis (Comparative Study)
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The research aims to answer the questions that revolve in the mind of mankind about how to create creation, how it existed prior to creation, who created existence, and the characteristics of that presence. The researcher also wanted to show that the culture of Imam Ali (peace be upon him) In the book of Adam, peace be upon him, God has punished Adam (peace be upon him) for not having sinned. Because his wife is the one who fed him the fruit of the tree, and this is contrary to what was stated in the sermon of Imam (peace be upon him) who Z Adam (peace be upon him) is the one who trusted Satan and Gwighth.We note that the approach of the rhetoric has pointed to the creation of angels and did not refer to the creation of Eve and the class

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Publication Date
Thu Mar 30 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Preliminary Cytotoxic Study of Some Novel Furo-2-quinolone Compounds
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In this research, new series of Furo-2-quinolone [FQ] compounds have been synthesized. These novel [FQ] compounds were prepared from coumarin derivatives (Furocoumarins: psoralen and isopsoralen).Identifications of these FQ compounds were performed by using infrared spectrum (I.R), Ultraviolet spectrum (U.V) and Nuclear Magnetic Resonance spectrum (H1-NMR) besides some physical data. The cytotoxic screening involves ;using HEP-2 cell line which gave differential responses against tested compounds : 4,6 Dimethyl furo[2, 3-g] coumarin (C1), 1-(2`, 4`, Dimethoxy benzylideneimino)-2,6-dimethyl Furo [2, 3-g] quinoline-2-one (C3) and the angular psoralen of the same derivative

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