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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 May 01 2018
Journal Name
Journal Of Engineering
Design of an Optimal Integral Backstepping Controller for a Quadcopter
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In this paper, an Integral Backstepping Controller (IBC) is designed and optimized for full control, of rotational and translational dynamics, of an unmanned Quadcopter (QC). Before designing the controller, a mathematical model for the QC is developed in a form appropriate for the IBC design. Due to the underactuated property of the QC, it is possible to control the QC Cartesian positions (X, Y, and Z) and the yaw angle through ordering the desired values for them. As for the pitch and roll angles, they are generated by the position controllers. Backstepping Controller (BC) is a practical nonlinear control scheme based on Lyapunov design approach, which can, therefore, guarantee the convergence of the position tracking

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Publication Date
Thu Sep 01 2022
Journal Name
Iraqi Journal Of Physics
Electrical Properties of PAN/PMMA Blends Doped with Lithium Salts
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         Polymer blended electrolytes of various concentrations of undoped PAN/PMMA (80/20, 75/25, 70/30, 65/35 and 60/40 wt%) and doped with lithium salts (LiCl, Li2SO4H2O, LiNO3, Li2CO3) at 20% wt have been prepared by the solution casting method using dimethylformamide as a solvent. The electrical conductivity has been carried out using an LCR meter. The results showed that the highest ionic conductivity was 2.80x10-7 (Ω.cm)-1 and 1.05x10-1 (Ω.cm)-1 at 100 kHz frequency at room temperature for undoped (60% PAN + 40% PMMA) and (80% PAN + 20% PMMA) doped with 20%wt Li2CO3 composite blends, respect

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Publication Date
Sat Oct 20 2018
Journal Name
Journal Of Economics And Administrative Sciences
Solve the problem of assignment by using multi-Objective programming
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he assignment model represents a mathematical model that aims at expressing an important problem facing enterprises and companies in the public and private sectors, which are characterized by ensuring their activities, in order to take the appropriate decision to get the best allocation of tasks for machines or jobs or workers on the machines that he owns in order to increase profits or reduce costs and time As this model is called multi-objective assignment because it takes into account the factors of time and cost together and hence we have two goals for the assignment problem, so it is not possible to solve by the usual methods and has been resorted to the use of multiple programming The objectives were to solve the problem of

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Publication Date
Tue Nov 01 2022
Journal Name
Japanese Dental Science Review
Pathogenesis of periodontitis – A potential role for epithelial-mesenchymal transition
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Publication Date
Wed Jun 01 2022
Journal Name
International Dental Journal
A Survey of Systemic Antibiotic Prescription Patterns Amongst Iraqi Dentists
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Publication Date
Mon Jan 01 2018
Journal Name
Fuel
Wettability of nanofluid-modified oil-wet calcite at reservoir conditions
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Nanofluids, liquid suspensions of nanoparticles (Np), are an effective agent to alter the wettability of oil-wet reservoirs to water-wet thus promoting hydrocarbon recovery. It can also have an application to more efficient carbon storage. We present a series of contact angle (θ) investigations on initially oil-wet calcite surfaces to quantify the performance of hydrophilic silica nanoparticles for wettability alteration. These tests are conducted at typical in-situ high pressure (CO2), temperature and salinity conditions. A high pressure–temperature (P/T) optical cell with a regulated tilted surface was used to measure the advancing and receding contact angles at the desired conditions. The results showed that silica nanofluids can alte

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Publication Date
Wed Jan 01 2020
Journal Name
Technologies And Materials For Renewable Energy, Environment And Sustainability: Tmrees20
Capitalized effect of gamma radiation on blood thinning drug (Aspirin)
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n this work, the effect of gamma rays on blood thinning drugs was studied using the drug (Aspirin), where gamma rays were spread with the drug using a radioactive source (Co60), and 15,000 grams of Aspirin were placed in the device (gamma chamber 900). The drug was subjected to different irradiation doses (5 KGy, 10 KGy, 15 KGy) and the amount of absorption of the drug was observed in the gamma for different doses and the study of x-rays. After confirming the absorption of the drug to radiation, the effect of the drug on blood thinning was calculated using the rat model and compared with the same drug and the same dose but without exposing the drug to radiation and comparing all results with the control group. The way drugs absorbed radiati

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Publication Date
Sat Apr 06 2019
Journal Name
International Journal Of English Linguistics
A Morpho- Syntactic study of Contemporary Science Fiction Short Stories
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The aim of the present study is to research two morphological processes: acronym and compounding (phrasal compounds/ circumlocution) and one syntactic category which are 'existential sentences' in science fiction short stories. The present paper identifies different types and rates of existential sentences. In this respect , 'bare existential and locative’ read the high percentages and may be contrasted with other classifications of English existential sentences which have a verb other than 'be' and a definite expression. 'Phrasal compounds' vary in rates as they constitute notable percentage for those that involve 'lexical means and lexical relations' followed by 'prepositional compounds' , 'conjunctional compounds' , and those invo

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Publication Date
Sun Oct 15 2023
Journal Name
Sumer 4
CYTOTOXIC IMPACT OF OUTER MEMBRANE NANOVESICLES (OMVS) ON OVARIAN CANCER
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This study focused on extracting the outer membrane nanovesicles (OMVs) from Escherichia coli BE2 (EC- OMVs) by ultracentrifugation, and the yield was 2.3mg/ml. This was followed by purification with gel filtration chromatography using Sephadex G-150, which was 2mg/ml. The morphology and size of purified EC-OMVs were confirmed by transmission electron microscopy (TEM) at 40-200 nm. The nature of functional groups in the vesicle vesicle was determined by Fourier transforms infrared spectroscopy (FT-IR) analysis. The antitumor activity of EC-OMVs was conducted in vitro by MTT assay in human ovarian (OV33) cancer cell line at 24,48 and 96hrs. The cytotoxicity test showed high susceptibility to the vesicles in ovarian compared to normal

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Publication Date
Thu Dec 01 2011
Journal Name
Iraqi Journal Of Physics
Electronic diagnostics system for the analysis of laser beam profile
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In this work the analysis of laser beam profile system ,using a two dimensional CCD (Charge Coupled Device) arrays, is established. The system is capable of producing video graphics that give a two dimensional image of laser beam. The video graphics system creates color distribution that represent the intensity distribution of the laser beam or the energy profile of the beam. The software used is capable of analyzing and displaying the profile in four different methods that is , color code intensity contouring , intensity shareholding, intensity cross section along two dimension x-y, and three dimensional plot of the beam intensity given in the same display.

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