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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
Thu Dec 01 2011
Journal Name
Swarm And Evolutionary Computation
Energy-aware evolutionary routing protocol for dynamic clustering of wireless sensor networks
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Publication Date
Fri Feb 01 2019
Journal Name
Journal Of Physics: Conference Series
Study the Antifungal Activity of ZnS:Mn Nanoparticles Against Some Isolated Pathogenic Fungi
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An aqueous chemical reaction has been used to prepare antifungal ZnS: Mn nanostructures, from manganese chloride, zinc acetate and thioacetamide in aqueous solution. The nanoparticle size has been controlled using thioglycolic acid as a capping factor. The major feature of the ZnS:Mn nanoparticles of average diameter ~ 2.73 nm is that possible preparing the sample from sources non-toxic precursors. The manufactured ZnS:Mn nanoparticles were identified and characterized to investigate the structure, morphology, composition of components of the nanoparticles and optical properties using (XRD, SEM, EDS and UV-Vis spectroscopy) techniques respectively. The agar dilution mechanism used to evaluate of the antifungal activity using ZnS:Mn nanopart

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Publication Date
Fri Oct 01 2010
Journal Name
Iraqi Board For Medical Specializations In Dermatology And Venereology
Treatment of Cutaneous Leishmaniasis by Topical 25% Podophyllin Solution (Case-Controlled Study)
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KE Sharquie, AA Noaimi, AG Al-Ghazzi, 2010 - Cited by 2

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Publication Date
Sat Dec 31 2016
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Experimental Investigation of Mass Transfer for Copper Reduction by Weight Difference Technique
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An experimental analysis was included to study and investigate the mass transport behavior of cupric ions reduction as the main reaction in the presence of 0.5M H2SO4 by weight difference technique (WDT). The experiments were carried out by electrochemical cell with a rotating cylinder electrode as cathode. The impacts of different operating conditions on mass transfer coefficient were analyzed such as rotation speeds 100-500 rpm, electrolyte temperatures 30-60 , and cupric ions concentration 250-750 ppm. The order of copper reduction reaction was investigated and it shows a first order reaction behavior. The mass transfer coefficient for the described system was correlated with the aid of dimensionless groups as fo

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Publication Date
Thu Jun 01 2023
Journal Name
South Asian Journal Of Social Sciences & Humanities
The Impact of University Internal Environment, Development Talents on Sustainable Competitive Advantage.
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There is a need to make serious efforts For Iraqi universities to be in the ranks of advanced universities in the world. This requires attracting teaching talents and providing an incubating environment for them. Therefore, the objective of the research was to explore the influence of (the environment, the development of talents) on sustainable competitive advantages. The research followed the descriptive approach and used the quantitative analysis method. Almaqaal university is the field of study. The study sample size (of 76 people), from almaaqal university teachers, and the sample comprised the available staff specialized in the field of Teaching and research. The questionnaire was utilised as a data collection tool and (spss) program w

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Publication Date
Wed Jul 01 2020
Journal Name
2020 42nd Annual International Conference Of The Ieee Engineering In Medicine & Biology Society (embc)
Recurrent Fusion of Time-Domain Descriptors Improves EMG-based Hand Movement Recognition
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Publication Date
Wed Apr 05 2023
Journal Name
International Journal Of Interactive Mobile Technologies (ijim)
Computer Literacy with Skills of Seeking for Information Electronically among University Students
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Computer literacy is an urgent necessity for university students, given the rapid development in the means of communication in which we live in this era, and the flow of abundant information. Mainly on the computer in all administrative and academic transactions, where first of all the registration for the semester is done through the computer. Computer culture has many characteristics and advantages that distinguish it from other sciences, including the concept of computer culture that cannot be defined absolutely, and it is difficult to define its levels, because the specifications of the computer-educated individual differ from one individual to another, and from time to time also, you find it a luxury in a country What, and you

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Publication Date
Thu Mar 01 2018
Journal Name
2018 Tenth International Conference On Advanced Computational Intelligence (icaci)
On low-level control strategies of lower extremity exoskeletons with power augmentation
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Publication Date
Tue Jun 15 2021
Journal Name
Al-academy
Rhetorical connections to the head-covers of Mesopotamian gods: جهينة حامد حساني
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The Rafidian artist discussed the headdresses of his idols with a varied scholarly momentum, so each idol had its own cover as this door of diversity contributed to the enrichment of Rafidian thought and full knowledge of their ideas and beliefs consistent with their multiple symbolic connections such as architecture, for example. The previous one, if not its entirety.
A research such as this (the discursive connections to the head-covers of the deities of the Mesopotamian civilization) aims to clarify the confusion that occurs through four chapters: The first chapter included: the research problem, the importance of research and the need for it, the objectives of the research, the temporal, spatial and objective limits of research, a

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Publication Date
Thu Oct 14 2021
Journal Name
Iraqi Journal Of Physics
Investigation of nonlinear optical properties for laser dyes-doped polymer thin film
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Solutions of dyes Rhodamine 6G (Rh6G) and Coumarin480(C480) were prepared at five concentrations (1x10-3, 5x10-4, 1x10-4, 5x10-5 and1x10-5) mol/l, the mixing was stirred to obtain on a homogenous solution, the(poly methyl-methacrylate) (PMMA) was solved by chloroform solvent with certain ratio, afterward (PMMA+Rh6G) and (PMMA+C480) thin films were prepared by casting method on glass block which has substrate with dimensions (7.5 x2.5)cm2, the prepared samples were left in dark place at room temperature for 24 hours to obtain uniform and homogenous thin films. UV-VIS absorption spectra, transmission spectra and fluorescence spectra were done to measure linear refractive index and linear absorption coefficient. The nonlinear optical proper

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