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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
Fri Apr 01 2022
Journal Name
Civil Engineering Journal
Prediction of Urban Spatial Changes Pattern Using Markov Chain
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Urban land uses of all kinds are the constituent elements of the urban spatial structure. Because of the influence of economic and social factors, cities in general are characterized by the dynamic state of their elements over time. Urban functions occur in a certain way with different spatial patterns. Hence, urban planners and the relevant urban management teams should understand the future spatial pattern of these changes by resorting to quantitative models in spatial planning. This is to ensure that future predictions are made with a high level of accuracy so that appropriate strategies can be used to address the problems arising from such changes. The Markov chain method is one of the quantitative models used in spatial planning to ana

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Publication Date
Thu Sep 30 2010
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
PREDICTION OF FINITE CONCENTRATIONBEHAVIOR FROM INFINITE DILUTION EGUILIBRIUM DATA
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Experimental activity coefficients at infinite dilution are particularly useful for calculating the parameters needed in an expression for the excess Gibbs energy. If reliable values of γ∞1 and γ∞2 are available, either from direct experiment or from a correlation, it is possible to predict the composition of the azeotrope and vapor-liquid equilibrium over the entire range of composition. These can be used to evaluate two adjustable constants in any desired expression for G E. In this study MOSCED model and SPACE model are two different methods were used to calculate γ∞1 and γ∞2

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Publication Date
Tue Sep 03 2019
Journal Name
Eastern-european Journal Of Enterprise Technologies
Prediction of spot welding parameters using fuzzy logic controlling
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Publication Date
Tue Jun 01 2021
Journal Name
Journal Of Engineering
Evaluation of Using Magnetized Water in Leaching Salts in Sandy Loam Soil
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Many studies and researchers have reported significant evidence that some physical properties of water can be changed as it passes through a magnetic field that can improve water use.  This can have a promising potential for applications, especially in the fields of irrigation and drainage. In this research, magnetized water was used to leach salt-affected sandy loam soil. A test rig was designed and constructed to investigate the effects of magnetized water on leaching soil. The rig consists of a magnetization device that can provide variable intensity. Water was supplied from a constant head reservoir to the magnetization device then to the soils that were placed in plastic columns. Five different magnetic intensi

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Publication Date
Fri Aug 28 2020
Journal Name
Iraqi Journal Of Science
Callus Induction and Shoot Formation for Mexican Red Bean (Phaseolus vulgaris L.) Pinto Cultivar in Vitro
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The current study aimed to adopt a method for inducing callus cells and regenerating the important common red bean using different types of growth regulators such as N6-benzylaminopurine (BAP), Naphthalene acetic acid (NAA), and Thidiazuron (TDZ). Different types of common bean pinto cultivar explants, such as internodes, cotyledons and roots, were inoculated on Murashige and Skoog medium (MS) provided with different combinations of plant growth regulators, including 1- BAP (5 mg/l) 2-BAP (4.5 mg/l) NAA (0.5 mg/l), 3- BAP (4.5 mg/l), and TDZ (0.1mg/l). Callus was initiated on MS culture medium supplied with 5 mg/l BAP for all explants (internodes, cotyledons, and roots) at 50, 20, and 10% respectively, while adding NAA with 0.5mg/l showed

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Publication Date
Sat Apr 01 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
In Vitro Release Study on Capsules and Tablets Containing Enteric - Coated Granules Prepared by Wet Granulation
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Wet granulation method was used instead of conventional pan coating  or fluidized –bed coating technique to prepare enteric-coated diclofenac sodium granules, using ethanolic solution of EudragitTM L100 as coating, binding and granulating agent .Addition of PEG400 or di-n-butyl phthalate as a plasticizer was found to improve the enteric property of the coat.

Part of the resulted granules was filled in hard gelatin capsules (size 0), while the other part was compressed into tablets with and without disintegrant.

The release profile of these two dosage forms in 0.1N HCl (pH 1.2)for 2 hours, and in phosphate buffer (pH 6.8) for 45 minutes as well as the release kinetic were compared with that of the en

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Publication Date
Wed Oct 17 2018
Journal Name
Iraqi Journal Of Laser
The Effect of using 940 nm Diode Laser in Comparison with Endoactivator on Radicular Dentin Permeability and Smear Layer Removal (An in Vitro Study)
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Abstract: The aim of this study is to assess the effectiveness of 940 nm diode laser in comparison to Endoactivator in elimination of smear layer in terms of radicular dentin permeability and ultra-structural changes of root canal walls by SEM evaluation. Twenty-eight single-rooted extracted lower premolars were instrumented up to size X4 (protaper Next, Dentsaply) and divided into two experimental groups according to the irrigation system, G1; activated by EndoActivator and G2; activated by Diode laser 940 nm, CW mode, 1.7 W. Afterward, the roots were made externally impermeable, filled with 2%methylene blue dye, divided horizontally into three segments representing the apical, middle, and coronal thirds then examined under stereo- micr

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Publication Date
Wed Oct 17 2018
Journal Name
Journal Of Economics And Administrative Sciences
Impact of evaluation of investment projects in achieving competitive strategy
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The aim of the research is to determine the impact of evaluation of investment projects after the preparation of investment budgets taking into consideration within the investment budgets the concept of competitive strategy, as the harmony between the preparation of investment budgets and competitive strategy will contribute to the success of economic unity and achieve profits well and achieve a competitive advantage. Strategies for economic units because the most important factor to them is the costs produced and the progress of the research problem is focused on "Is it possible to include a strategy of competition, especially within the investment budget when prepared The study concluded that the investment plan prepared by the

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Publication Date
Wed Aug 05 2026
Journal Name
Journal Of Baghdad College Of Dentistry
A Comparison of the Effectiveness of Reciprocating System with Continuous Rotary Systems in Non-Surgical Endodontic Retreatment (An In vitro study)
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Background: Optimal root canal retreatment was required safe and efficient removal of filling material from root canal. The aim of this in vitro study was to compare the efficacy of reciprocating and continuous motion of four retreatment systems in removal of root canal filling material. Materials and Methods: Forty distal roots of the mandibular first molars teeth were used in this study, these roots were embedded in cold clear acrylic,roots were instrumented using crown down technique and rotary ProTaper systemize Sx to size F2 ,instrumentation were done with copiousirrigation of 2.5% sodium hypochlorite and 17% buffered solution of EDTA was used as final irrigant followed by distilledwater, roots were obturated with AH26 sealer and Prota

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Publication Date
Tue Mar 01 2016
Journal Name
Journal Of Baghdad College Of Dentistry
A Comparison of the Effectiveness of Reciprocating System with Continuous Rotary Systems in Non-Surgical Endodontic Retreatment (An In vitro study)
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Background: Optimal root canal retreatment was required safe and efficient removal of filling material from root canal. The aim of this in vitro study was to compare the efficacy of reciprocating and continuous motion of four retreatment systems in removal of root canal filling material. Materials and Methods: Forty distal roots of the mandibular first molars teeth were used in this study, these roots were embedded in cold clear acrylic,roots were instrumented using crown down technique and rotary ProTaper systemize Sx to size F2 ,instrumentation were done with copiousirrigation of 2.5% sodium hypochlorite and 17% buffered solution of EDTA was used as final irrigant followed by distilledwater, roots were obturated with AH26 sealer and Prota

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