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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 Mar 01 2026
Journal Name
Journal Of Baghdad College Of Dentistry
An Assessment of Alpha-Amylase as Salivary Psychological Stress Marker in Relation to Temporomandibular Disorders among a Sample of Dental Students
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Background: University dental students perceived a higher level of stress prior to the final exam associated with raised salivary alpha-amylase levels which could be considered as a useful noninvasive biomarker for measuring acute stress. Using a Helkimo anamnestic and clinical dysfunction scoring for temporomandibular disorders can give a better insight about the association of this marker and temporomandibular disorders. The aim of this study was to evaluation level of salivary alpha-amylase in stressor students with temporomandibular disorders and the relation between the marker in relation to temporomandibular disorders severity. This might give a better understanding to the role of psychological stress as an etiological factor for deve

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Publication Date
Sat May 01 2010
Journal Name
Journal Of Baghdad College Of Dentistry
Comparison of microleakage Restorative Dentistry Comparison of microleakage in three different retrograde cavity preparations with Mineral Trioxide Aggregate as filling material
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Background: The apical seal is the single most important factor in determining the success of surgical endodontics, the aim of this study was to compare the sealing ability of Mineral Trioxide Aggregate in three different cavity designs. Materials and Methods: Thirty extracted human single-rooted teeth were divided into three groups of ten teeth per group, a retrograde cavity preparation was carried out using a low speed handpiece and round bur with parallel walls in the first group, ultrasonic retrotip and unit in the second group and a low speed handpiece with a carbide inverted cone bur with undercuts in the third group, all the cavities were filled with MTA. microleakage was measured by dye penetration technique using methylene blue. Re

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Publication Date
Sun Sep 15 2019
Journal Name
Al-academy
Use of the Iraqi Song in the Orchestral Compositions of Hanz Moomer- (Foug Al-Nakhl) as a Model: فراس ياسين جاسم
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The use of the Iraqi song in the symphony orchestra is one of the pioneering and important works, which carries with it an artistic value of aesthetic specificity in how to use the Iraqi singing heritage. The research aimed to identify the employment of the song (Foug Al-Nakhl) and its works within the Iraqi national symphony orchestra music by the author Hans Count Momer whose works still have a great influence on the authors of the Iraqi orchestra.  The researcher presented a brief introduction to the Iraqi Symphony Orchestra, a brief introduction about the author, and the trends of world music towards heritage. He also talked about musical composition, research procedures and tools, and applying the tool to the selected sample (F

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Publication Date
Sat Dec 01 2018
Journal Name
Al-khwarizmi Engineering Journal
A study of Land Zoning in the base of Traffic Noise Pollution Levels using ArcGIS: Kirkuk City as a Case Study
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This study is an approach to assign the land area of  Kirkuk city [ a city located in the northern of Iraq, 236 kilometers north of  Baghdad  and 83 kilometers  south of  Erbil [ Climatic atlas of  Iraq, 1941-1970  ]  into different  multi zones by using Satellite image and Arc Map10.3,  zones of different traffic noise pollutions. Land zonings process like what achieved in this paper will help and of it’s of a high interest point for the future of Kirkuk city especially urban

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Publication Date
Sun Aug 30 2020
Journal Name
Journal Of Economics And Administrative Sciences
Financial Innovation as an Entrance to Sustainable Financing A Case Study of Islamic Banks in the State of Qatar (2014-2018)
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While the impact of the fourth Industrial Revolution on the economy keeps accelerating, the signs of the fifth industrial revolution, whose key is innovation and creativity started to evolve. However, the challenge of achieving sustainable development and its goals remains faced by the global organizations; In this situation, Islamic banks are exposed to many challenges among which is the challenge of keeping themselves abreast of the latest developments in the modern technology which in turn is a tool for continuity and competition. On the flip side, to avoid the negative impact that these changes can have such as an increased gap between financial innovations and the requirements of sustainable development. Islamic banks in the

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Publication Date
Sun Sep 01 2019
Journal Name
Journal Of Global Pharma Technology
Calculation of Stabilization Energy of Tetrahedrane with its Nitrogen Substituted Derivatives by DFT Method and Driving an Empirical Relation Connect it with Charge Functions of the Molecule
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In this work the strain energy of tetrahedrane and its nitrogen substituted molecules were calculated by isodesmic reaction method according to DFT quantum chemical fashion, the used basis set was 6-31G/B3-LYP, in addition all structures were optimized by RM1 semi-empirical method. From the obtained data we estimate an empirical equation connect between strain energy of the molecule with charge functions represented by dipole moment of the molecule plus accumulated charge density involved within the tetrahedron frame plus the number of nitrogen atoms. The results indicate the charge spreading factors by polarization and processes are the most important factors in decreasing the strain energy.

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Publication Date
Thu Jan 01 2015
Journal Name
Advances In Life Science And Technology
Polycondensation of Ethylenediaminetetraacetic Acid with Some Prepared Diamines Derived from Amino Acids or Antibiotic
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Many condensed polymers [A1-A7] were prepared via reaction of (Ethylenediaminetetraacetic acid = EDTA), with different prepared imide-diamines by modification [ modification of amino acids and antibiotics (B1- B7)] Imide-diamines were prepared by chlorination of L-amino acids such as [ L-Histidine, L-Alanine, L-Valine, L-Glycine and L-Aspargine ] or selected antibiotics such as [Cephallixine monohydrate and Amoxilline ] with thionyl chloride at 0°C, then reacted with ammonia to obtain imidediamines [B1-B7] . The physical properties of all prepared condensed polymers [A1-A7], new prepared diamines [B1-B7] were studied and characterized by FT -IR spectroscope to certify the structural formulas. The thermal analysis (TGA, DTA) were studied, a

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Publication Date
Tue Jan 01 2019
Journal Name
Journal Of Colloid And Interface Science
Organic acid concentration thresholds for ageing of carbonate minerals: Implications for CO2 trapping/storage
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Hypothesis CO2 geological storage (CGS) involves different mechanisms which can store millions of tonnes of CO2 per year in depleted hydrocarbon reservoirs and deep saline aquifers. But their storage capacity is influenced by the presence of different carboxylic compounds in the reservoir. These molecules strongly affect the water wetness of the rock, which has a dramatic impact on storage capacities and containment security. However, precise understanding of how these carboxylic acids influence the rock’s CO2-wettability is lacking. Experiments We thus systematically analysed these relationships as a function of pressure, temperature, storage depth and organic acid concentrations. A particular focus was on identifying organic acid conce

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Publication Date
Thu Sep 29 2022
Journal Name
Al–bahith Al–a'alami
Digital media and linguistic evaluation between the need to stay and the idea of dispensing
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In spite of the contemporary development over the world in pertaining of modernization and its differences about the transformation of the knowledge but, the important instrument to transfer the thoughts and information did not have change except the language. So the evolutionary process became as a torrent or fusillade above the cliff which drifted anything. So that the objective inquiry and impressed with varieties of development the casement to evaluate the linguistic or re - correction highlight article in order to preserve on the origins of the language and its sobriety.
Today, we have different correspondence and social media as

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Publication Date
Tue Mar 28 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Formulation and Evaluation of Bilayer Tablets Containing Immediate Release Aspirin Layer and Floating Clopidogrel Layer
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Aspirin and clopidogrel are considered the most important oral platelets aggregation inhibitors. So it is widely used for treatment and prophylaxis of cardiovascular and peripheral vascular diseases related to platelets aggregation .In this study aspirin and clopidogrel were formulated together as floating bilayer tablet system. Three different formulas of 75 mg aspirin were prepared by wet granulation method as immediate release layer; different disintegrants used to achieve rapid disintegration. Formula with crosscarmellose as disintegrant achieve rapid disintegration was selected for preparation of bilayer tablet.

Different formulas of 75 mg clopidogrel were prepared as sustained release floating layer by wet granulation (effe

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