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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 Jun 30 2020
Journal Name
College Of Islamic Sciences
Novelist character in the Iraqi press criticism – Fadhil Thamir as a model))
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The novel has recently received great attention from readers and before them writers, due to the role it is playing, and this indicates an important rule, which is whenever there is art or creativity, there must be a criticism of its own, and this criticism is certainly no less important than its owner, so we find There are critics who have their distinguished literary position in following up the narrative development, and trying to describe the transformation of its elements, including Professor Fadel Thamer, and whoever wants to approach an element of the novel as an explorer, he must stand on the visions of this critic about it, and this is what made us take the element (personality) Tracking the most important opinions of the critic

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Publication Date
Wed Jun 01 2022
Journal Name
Journal Of The College Of Languages
The Multifunctional Morphemes in Kurdish Language the Morpheme Le as an example
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Kurdish language multifunctional morphemes indicate the different functional morphological, syntactical, and semantic tasks of the morphemes. The present study discusses the multifunctional task of the Morpheme Le in Kurdish Language. The Morpheme Le has marginally been included in other studies, yet up to the present times, there has not been a research inclusively dedicated to thoroughly discuss and clarify its multifunctional aspects. The present study is divided into two chapters: Chapter one discusses the theoretical aspect of chapter two that is entirely concerned with the practical aspect of the morpheme Le. The first part of chapter one sheds light on the morphological aspect of the morpheme while part two discusses

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Publication Date
Tue Mar 01 2016
Journal Name
Journal Of Engineering
Critical Success Factors in Construction Projects (Governmental Projects as a Case Study)
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The importance of the construction sector and its Great role in the provision of services and infrastructure, reduce poverty, improve living conditions and improve the economic situation in the country, impose attention to the way in which the projects implemented for its improvement and to get successful projects. The objective of this research was to determine the criteria for success as well as critical success and failure factors that have a significant impact on project success. A selected 75 engineer (department managers, project managers and engineers) are asked to fill  the questionnaire form, Sixty-seven valid questionnaire forms were analyzed statistically to get search results, which were as follows : Twe

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Publication Date
Thu Feb 25 2021
Journal Name
Iraqi Journal Of Agricultural Sciences
ROSEMARY VOLATILE OIL AS A PRESERVATIVE AGENT IN SOME CANNED MEAT FOODS
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This research was aimed to evaluate activity of Rosemary volatile oil and Nisin A in vivo and on B. cereus isolated from some canned meat products in vitro. The results showed that the activity of Rosemary volatile oil (2000 µg/ml) and Nisin A (350 µg\ml) attained to 27 and 19 mm inhibitory zone diameter respectively in well diffusion method. The viable plate count from samples of canned meat treated with effective concentration of Rosemary volatile oil and Nisin A were examined. The samples with Rosemary volatile oil was not showed any CFU/g after 9 days of preservation while sample with Nisin A and control observed 49 and 45 CFU/g respectively. In vivo experiment on mice, two weeks after oral dose of Rosemary volatile oil (2000

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Publication Date
Sun Dec 01 2019
Journal Name
Iop Conference Series: Materials Science And Engineering
Place dependence as the physical environment role function in the place attachment
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Abstract<p>This research sheds light on the physical environment role in creating the place attachment, by discussing one of the important factors in the attachment creation, it is the concept place dependence, consisting of two important dimensions: the place quality and the place expectation; they contain a number of the supporter physical environment sub-indicators for place attachment. Eight physical indicators were reached; they were found to have a close relationship to the place attachment, including: the open and green spaces existence, land use diversity, diversity of housing types, dwelling / population density, accessibility, transport network development degree, transport multiple mo</p> ... Show More
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Publication Date
Tue Aug 02 2011
Journal Name
J. College Of Education / Al-mustansiriya University
Synthesis and characterization of mixed ligand complexes of some metals with ( L- phenylalanine and nicotinamide)
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This paper presents the synthesis and study of some new mixed-ligand complexes containing nicotinamide(C6H7N2O) symbolized (NA) and phenylalanine (C9H11NO2)symbolized (pheH)] with some metal ions. The resulting products were found to be solid crystalline complexes which have been characterized by :Melting points, Solubility, Molar conductivity. determination the percentage of the metal in the complexes by flame(AAS), magnetic susceptipibility, Spectroscopic Method [FT-IR and UV-Vis]. The proposed structure of the complexes using program , chem office 3D(2006) . The general formula have been given for the prepared complexes : [M(NA)2(phe)]cl M(II): Mn(II) ,Co(II) , Ni(II) , Cu(II) , Zn(II) , Cd(II) & Hg(II)). NA = Nicotinamide= C6

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Publication Date
Mon Aug 01 2016
Journal Name
Iraqi Journal Of Science
Synthesis, Characterization and Study of The Liquid Crystalline Behavior of Four and Six Heterocyclic Compounds
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The new compounds synthesized by sequence reactions starting from a reaction of 4-hydroxybenzaldehyde with 1,5-dibromo pentane to produce dialdehyde)I( .Then compound )I( reacted with different aromatic amines to give schiff bases )IIIV(,thereafter added acetyl chloride to schiff bases to yield N-acyl derivatives)VVII(.While1,3-diazetine derivatives)VIII-X( were synthesized from the reaction of N-acyl derivatives with sodium azide.The reaction of thiourea with N-acyl compounds led to formation of thiourea derivatives (XI-XIII).Finally, the pyrimidine compounds )XIV-XVI( were synthesized by ring closure reaction of compounds(XIXIII) with diethyl malonate.The synthesized compounds were characterized by measurements of melting points,FTIR,1H-N

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Publication Date
Sun Jan 01 2012
Journal Name
Al-mustansiriya J. College Of Education
Synthesis and characterization of mixed ligand complexes of some metals with ( L- phenylalanine and nicotinamide)
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This paper presents the synthesis and study of some new mixed-liagnd complexes containing nicotinamide(C6H7N2O) symbolized (NA) and phenylalanine (C9H11NO2)symbolized (pheH)] with some metal ions. The resulting products were found to be solid crystalline complexes which have been characterized by :Melting points, Solubility, Molar conductivity. determination the percentage of the metal in the complexes by flame(AAS), magnetic susceptipibility, Spectroscopic Method [FT-IR and UV-Vis]. The proposed structure of the complexes using program , chem office 3D(2006) . The general formula have been given for the prepared complexes :[M(NA)2(phe)]cl M(II): Mn(II) ,Co(II) , Ni(II) , Cu(II) , Zn(II) , Cd(II) & Hg(II) . NA = Nicotinamide= C6H7N2O Phe -

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Publication Date
Mon Jul 01 2024
Journal Name
Journal Of Food Process Engineering
Artificial intelligence‐based modeling of novel non‐thermal milk pasteurization to achieve desirable color and predict quality parameters during storage
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Abstract<sec><label></label><p>This study proposed using color components as artificial intelligence (AI) input to predict milk moisture and fat contents. In this sense, an adaptive neuro‐fuzzy inference system (ANFIS) was applied to milk processed by moderate electrical field‐based non‐thermal (NP) and conventional pasteurization (CP). The differences between predicted and experimental data were not significant (<italic>p</italic> > 0.05) for lightness (<italic>L</italic>*), redness‐greenness (<italic>a</italic>*), yellowness‐blueness (<italic>b</italic>*), total color differences (∆<italic>E</italic>), hue angle (<italic>h</italic></p></sec> ... Show More
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Publication Date
Sat Jan 01 2022
Journal Name
Applied Ecology And Environmental Research
EFFECT OF SPRAYING WITH FOLIC ACID AND YEAST EXTRACT ON THE GROWTH, YIELD AND CALCIUM OXALATE CONCENTRATION OF SPINACH (SPINACIA OLERACEA L.)
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