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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 Jan 01 2018
Journal Name
Journal Of Engineering And Applied Sciences
Estimation of concentration of radioactive elements for the Liquid Waste pool in radiochemistry laboratories in Al Tuwaitha site Baghdad-Iraq
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Scopus
Publication Date
Sun Jul 01 2018
Journal Name
Current Research In Microbiology And Biotechnology
Detection of anti-Helicobacter pylori in patients with Multiple Sclerosis
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To determine the relationship between Helicobacter pylori infection and Multiple Sclerosis (MS) disorder, 20 patients with MS aged (25-60) years have been investigated from the period of 2016/12/1 to 2017/3/1 and compared to 15 apparently healthy individuals. All study groups were carried out to measure anti H.pylori IgA and H.pylori IgG antibodies by enzyme linked immunosorbent assay (ELISA) technique. There was a significant elevation (p<0.05) in the concentration of anti H.pylori IgG and IgA antibodies (Abs) compared to control group, and there was no significant difference (p>0.05) in the concentration of IgA and IgG (Abs) of H.pylori according to gender, and there was no significant difference (p>0.05) in the concentration of IgA and I

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Publication Date
Sun Jun 01 2014
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
The Role of Stock Markets in the Anti-Money Laundering
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لم تعد ظاهرة غسل الأموال ظاهرةً محلیة أو إقلیمیة، فكل دولة معرضة لهذه الظاهرة لانتأثیراتها تستهدف الإنسان أینما كان باستهدافها الأوضاع الاقتصادیة والمالیة والاجتماعیة وحتىالأخلاقیة، سواء على المستوى الوطني أم على المستوي الدولي، فضلاً عن استغلال الاندماج الحاصلفي أسواق المال الدولیة والتطور التقني في الأنظمة المالیة لنقل الأموال المراد غسلها وتحریكها إلى إيمكان في العالم، وهو ما

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Publication Date
Thu Jan 24 2019
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
The Role of Commercial Banks in the Anti-Money Laundering
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Characteristic of money laundering phenomenon is a compound and complex nature like the style of regular crimes . These operations are planned and excuted with those who have high quality experiences to hide the evidences of their deeds so They ask the help of financials ,economicals and legists to plan for money laundering. Banks are important and suitable places for illegal circulation of money because of the different types of accounts , rapidity and overlap which emphasis of its main duty to dislocate illegal money which comes from illegal sources without adding legal characteristic to it . Here we should explain the important role of banks in striving the phenomenon –Bank should try to show and analyze inward proced

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Crossref
Publication Date
Thu Jun 01 2006
Journal Name
Journal Of The College Of Languages (jcl)
The Image of the Anti- Hero in James Joyce's Ulysses
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The hero traditionally has such admirable traits as courage, fortitude,
chivalry and patriotism. In the literary works, the hero is the leading
character and the pivot around which all the characters and the events
revolve. The characteristics of the hero usually reflect the cultural values
of his time. Because, in each age, Man's attitudes towards himself and the
world change, different images of the hero emerge.
In Greek Mythology, the hero is frequently favoured by the gods;
therefore, he is himself semi-divine. The Greek hero is of princely birth
and is endowed with good physique, exceptional strength, skill in
athletics and battle, energy and eloquence, like Odysseus who is the hero
of the Odyssey, long

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Publication Date
Wed Dec 18 2019
Journal Name
Baghdad Science Journal
Detection of Nutrients and Major Ions at Al Muthanna Storage Site Soil
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In the early 90s military operations and United Nations Special Commission “UNSCOM” teams have been destroyed the past Iraqi chemical program. Both operations led an extensive number of scattered remnants of contaminated areas. The quantities of hazardous materials, incomplete destructed materials, and toxic chemicals were sealed in two bunkers. Deficiency of appropriate destruction technology led to spreading the contamination around the storage site. This paper aims to introduce the environmental detection of the contamination in the storage site area using geospatial analysis technique. The environmental contamination level of nutrients and major ions such as sulphate (SO4), potassium (K), sodium (Na), magnesi

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Publication Date
Fri Jun 29 2018
Journal Name
Journal Of The College Of Education For Women
Stream of Consciousness Technique: Psychological Perspectives and Use in Modern Novel
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Stream of Consciousness technique has a great impact on writing literary texts in the modern age. This technique was broadly used in the late of nineteen century as a result of thedecay of plot, especially in novel writing. Novelists began to use stream of consciousness technique as a new phenomenon, because it goes deeper into the human mind and soul through involving it in writing. Modern novel has changed after Victorian age from the traditional novel that considers themes of religion, culture, social matters, etc.  to be a group of irregular events and thoughts interrogate or reveal the inner feeling of  readers.

This study simplifies stream of consciousness technique through clarifying the three levels of conscious

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Publication Date
Thu Sep 01 2016
Journal Name
Saudi Journal Of Pathology And Microbiology
Synthesis, Characterization and Antibacterial Activities of Mixed Ligand Complexes of Symmetrical Schiff Base and 8-Hydroxyquinoline with Zn(II), Cd(II) and Hg(II)
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The current work reports a new Schiff base [N1-benzylidenebenezene-1,2-diamine(L) = C20H16N2] has been synthesized from benzaldehyde (C6H5CHO) and O- aminoaniline (O-C6H4(NH2)2. Metal mixed ligand complexes of the Schiff base were prepared from chloride salts of Zn(II), Cd(II) and Hg(II) in ethanol and 8-hydroxyquinoline(8HQ)(C9H7NO) containing sodium hydroxide. All the complexes were characterized on the basis of their; FT-IR and U.V spectra, melting point, molar conductance, and determination of the percentage of the metal in the complexes by flame (AAS). In the all complexes, (8HQ) behaves as a bidentate ligand as primary ligand through –-OH phenolic group and –N groups of pyridine group. Also, the prepared ligand (L) was bidentate i

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Publication Date
Fri Apr 01 2022
Journal Name
Chemical Methodologies
Design, Synthesis of Imidazolone and Oxazepine Derivatives Bearing Imidazo (2, 1-b) Thiazole along with its Antimicrobial Activity
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A new methodology was applied to the synthesis of new imidazolones and oxyazepine derivatives containing imidazo thiazole fused rings. Starting with 5-(4-bromo phenyl) imidazo (2, 1-b) thiazole, which was synthesized using the standard procedure, the Carbaldehyed group was introduced at position 6 of 5-(4-bromo phenyl) imidazo (2, 1-b) thiazole. Then, this 6-carbaldehyed derivative was condensed with different substituted aromatic amines to afford new Schiff bases. The latter were cyclized into new oxazepine and imidazolone derivatives by using phthalic anhydride and glycine, respectively. These new derivatives were characterized by using FT-IR, 1HHNMR, and 13CNMR spectra, as well as examined (evaluated) for anti-bacterial and anti-fungal a

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Publication Date
Sun Mar 01 2026
Journal Name
Interdisciplinary Neurosurgery
Surgical outcomes and challenges in spinal cord tumor resection: a comparative study of elderly vs. young patients
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