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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
Mon Aug 01 2016
Journal Name
2016 38th Annual International Conference Of The Ieee Engineering In Medicine And Biology Society (embc)
Changes in the EEG amplitude as a biomarker for early detection of Alzheimer's disease
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The rapid increase in the number of older people with Alzheimer's disease (AD) and other forms of dementia represents one of the major challenges to the health and social care systems. Early detection of AD makes it possible for patients to access appropriate services and to benefit from new treatments and therapies, as and when they become available. The onset of AD starts many years before the clinical symptoms become clear. A biomarker that can measure the brain changes in this period would be useful for early diagnosis of AD. Potentially, the electroencephalogram (EEG) can play a valuable role in early detection of AD. Damage in the brain due to AD leads to changes in the information processing activity of the brain and the EEG which ca

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Publication Date
Thu Dec 01 2022
Journal Name
Baghdad Science Journal
The Effective M3Y Residual Interaction In 41Ca As a Nuclear Diffraction Grating of Electrons
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The total and individual multipole moments of  magnetic electron scattering form factors in 41Ca  have been investigated using a widely successful model which is the nuclear shell model configurations keeping in mind of 1f7/2 subshell as an L-S shell and Millinar, Baymann, Zamick as L-S shell (F7MBZ) to give the model space  wave vector. Also, harmonic oscillator wave functions have been used as wave function of a single particle in 1f7/2  shell. Nucleus 40Ca as core closed and Core polarization effects have been used as a corrective with first order correction concept to basic computation of L-S shell and the excitement energy has been implemented with 2ћω. The

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Publication Date
Wed Jan 30 2019
Journal Name
Journal Of The College Of Education For Women
The Linguistic Analysis of Deduction in The Holy Qur’an: Surat Ghafir as a Model
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This paper aims at discovering the real implication of deduction in the Arabic culture
with concentration on its applications in Arabic grammar, logic, and fundamentals of Islamic
legislations. Some light has been shed on deduction in the Arabic culture but most of recent
works did not analyze deduction according to the pragmatic analysis. This paper will answer
the following questions:
 to what extent deduction in Arabic grammar could comprehend with deduction l logic and
fundamentals of thinking in Islamic thought?
 how can we find the deduction thinking in the Qur’anic surah if Ghafir?
 Can we find parts of deduction in the surah?
The methodology in this paper is descriptive analytical. This metho

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Publication Date
Fri Apr 18 2014
Journal Name
Journal Of Advances In Chemistry
Anastatica Hierochuntica L. Used As an Alternative of Conjugated Estrogen (Premarin) in Rabbit Females
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There are risks and benefits with all medicines and estrogen replacement is no exception. In fact, estrogen replacement is one of the most controversial topics in Endocrinology. Anastatica hierochuntica L. is a popular treatment for the management of female reproductive disorders. The present research highlights the effect of aqueous extract of plant against conjugated estrogen(Premarin) in rabbits. Femal oryciolagus cuniculus rabbits were divided into four groups: the 1 st group, rabbits were orally administered (using a feeding solution )with daily dose(5 mL distilled water)for two months, the 2nd group, the rabbits were treated with conjugated estrogen (50 µg/kg b.w, body weight )for one month. The 3rd group, the rabbits were treated w

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Publication Date
Sat Jun 30 2018
Journal Name
College Of Islamic Sciences
Narrative narration in the poetry of Mohammed Abdul Muttalib   (Top poem as a model)
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Poets of the age since ancient times to recount the events of their adventures in a fun story style in which the elements of the story of personalities, time and place, and we do not mean this modern art technique (poetic story) as it is now, but was aimed at the pleasures of the other receiving because it is the rule of the quality of literary output, Other times the narrative of events inspired by his broad imagination and this mixing indicates the story's involvement with Arabic poetry to be (poetic story) and this depends entirely on addressing the poet to the recipient, and requires in this narrative to be familiar with the elements of influence and suspense in the other or turned into a monotonous and dull narrative Influential, un

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Publication Date
Fri Dec 15 2023
Journal Name
Al-academy
Phenomenology as an approach to seeing the aesthetics of ugliness in contemporary art designs
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With a descriptive and analytical approach, it discusses the concept of phenomenology as an approach to seeing the aesthetics of ugliness as one of the concepts associated with the aesthetic experience in contemporary art designs, as it is the result of communication between artistic production and the recipient, which leads to creating a state of aesthetic pleasure. A phenomenological method is used to uncover the aesthetics of ugly and to connect ugliness and beauty since ugliness in aesthetics incorporates beauty as a modern aesthetic vision from the phenomenological perspective. The study investigated aesthetics as a phenomenon of perception, sensory knowledge, and the aesthetic response to the production of designs in contemporary a

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Publication Date
Tue Jan 12 2021
Journal Name
Systematic Review In Pharmacy
CUPPER(||)AND MERCURY (||)Complexes WITH SCHIFF BASE LIGAND FROM BENZIDIN WITH ISATIN AND BENZOIN:SYNTHESIS,SPECTRAL CHARACTERIZATION, THERMAL STUDIES AND BIOLOGICAL ACTIVITIES
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CUPPER(||)AND MERCURY (||)Complexes WITH SCHIFF BASE LIGAND FROM BENZIDIN WITH ISATIN AND BENZOIN:SYNTHESIS,SPECTRAL CHARACTERIZATION, THERMAL STUDIES AND BIOLOGICAL ACTIVITIES

Publication Date
Wed Mar 10 2021
Journal Name
Baghdad Science Journal
synthesis of poly condensation
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in the present investigation new eight poly esrers as schiff bases wich containing pendant imine group were synthesized by treatment of poly acryloyl chlodire with ethanol amine group were synthesized by treatment of poly acryloyl chloride with ethanol

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Publication Date
Mon Jul 10 2023
Journal Name
Journal Of Engineering
Rhythm As Creative System In Houses Architecture Comparative Application Study Between Heritage And Contemporary Houses
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Rhythm is considered one of the creative concepts in the recent architectural thought; it has emerged clearly as a mean of creating the highest levels of creativity in architecture, especially in contemporary architectural movements. The importance of rhythm has  emerged, especially, when the architecture , its beginnings concentrated on the principle of the links with poetic structures. Many architectural studies deal with concept of rhythm in architecture with different ways various according to the trend of each study, this show the importance of studying the concept of rhythm in the architectural field in general. This study try to focus on the utilization of rhythm as creative system in architecture of heritage and contemporary

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Publication Date
Wed Aug 01 2018
Journal Name
Ecotoxicology And Environmental Safety
Biochemical and molecular alterations in freshwater mollusks as biomarkers for petroleum product, domestic heating oil
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