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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
Wed Sep 16 2015
Journal Name
Journal Of The College Of Basic Education
Formation of self-assembled polymeric complexes with bridged azido-dicarboxylato ligands
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In this publication, several six coordinate bridged-polymeric metal complexes are reported. The reaction of 4,4`-dipyridine with ethyl chloroacetate in mole ratio of 1:2 gave the multidentate carboxylate ligand bis(N-carboxylatomethyl)-4,4`-dipyridinium). The reaction of the ligand with metal chloride and sodium azide resulted in the formation of the required polymeric complexes. Upon complex formation, the carboxylato ligand behaves as a neutral multidantate species. The mode of bonding and overall geometry of the complexes were determined through physicochemical and spectroscopic methods. These studies revealed octahedral geometry about metal centres and complexes of the general formula [Cr2(L)(N3)4]Cl2.H2O, Na2[Ag2(L)(N3)4].H2O and [M2(L

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Publication Date
Fri Nov 25 2022
Journal Name
Tem Journal
Preparing of ECG Dataset for Biometric ID Identification with Creative Techniques
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The Electrocardiogram records the heart's electrical signals. It is a practice; a painless diagnostic procedure used to rapidly diagnose and monitor heart problems. The ECG is an easy, noninvasive method for diagnosing various common heart conditions. Due to its unique advantages that other humans do not share, in addition to the fact that the heart's electrical activity may be easily detected from the body's surface, security is another area of concern. On this basis, it has become apparent that there are essential steps of pre-processing to deal with data of an electrical nature, signals, and prepare them for use in Biometric systems. Since it depends on the structure and function of the heart, it can be utilized as a biometric attribute

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Publication Date
Fri Oct 01 2010
Journal Name
J Saudi Soc Dermatol Dermatol Surg
Outbreak of Thallium poisoning among Iraqi Patients: A case descriptive study
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KE Sharquie, GA Ibrahim, AA Noaimi, HK Hamudy, J Saudi Soc Dermatol Dermatol Surg, 2010 - Cited by 2

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Publication Date
Sun Jun 01 2014
Journal Name
Journal Of Water Resource And Hydraulic Engineering (jwrhe)
Large Scale Field Physical Model Simulation of Roseires Dam-Break, Sudan
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Physically based modeling approach has been widely developed in recent years for the simulation of dam failure process due to the lack of field data. This paper provides and describes a physically-based model depending on dimensional analysis and hydraulic simulation methods for estimating the maximum water level and the wave propagation time from breaching of field test dams. The field physical model has been constructed in Dabbah city to represent the collapse of the Roseires dam in Sudan. Five cases of a dam failure were studied to simulate water flood conditions by changing initial water height in the reservoir (0.8, 1.0, 1.2, 1.4 and 1.5 m respectively).The physical model working under five cases, case 5 had the greatest influence of t

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Publication Date
Thu Sep 01 2022
Journal Name
Physical Chemistry Research
Dielectric Properties of Ultra-Low Dielectric Constant PVA-Pentaerythritol/MnO2 Nanocomposite
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this work, a simple method was used to prepare the MnO2 nanoparticles. These nanoparticles then were characterized by several techniques, such as X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy (SEM) and atomic force microscope (AFM). The results showed that the diffraction peak of MnO2 nanoparticles was similar to that of standard data. The images of AFM and SEM indicated that the MnO2 nanorods were growing from the MnO2 nano spherical shape. PVA-pentaerythritol/MnO2 nanocomposite films were fabricated by evaporating casting method. The dielectric constant and loss tangent of P-Ery/MnO2 films were measured between 10 kHz and 1 MHz using LCR. As the content of MnO2 increased, the dielectric constant

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Publication Date
Sat Jul 22 2023
Journal Name
Journal Of Engineering
Investigation Parameters of Resistance Spot Welding For AA1050 Aluminum Alloy Sheets
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The parameters of resistance spot welding (RSW) performed on low strength commercial aluminum sheets are investigated experimentally, the performance requirements and weldability issues were driven the choice of a specific aluminum alloy that was AA1050. RSW aluminum alloys has a major problem of inconsistent quality from weld to weld comparing with welding steel
alloys sheet, due to the higher thermal conductivity, higher thermal expansion, narrow plastic temperature range, and lower electrical resistivity. Much effort has been devoted to the study of describing the relation between the parameters of the process (welding current, welding time, and electrode force) and weld strength. Shear-tensile strength tests were performed to ind

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Publication Date
Sat Apr 09 2022
Journal Name
Engineering, Technology & Applied Science Research
Static Shear Strength of a Non-Prismatic Beam with Transverse Openings
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In this study, a predicated formula is been proposed to find the shear strength of non-prismatic beams with or without openings. It depends on the contributions of concrete shear strength considering the beam depth variation and existing openings, shear steel reinforcements and defines the critical shear section, the effect of diagonal shear reinforcement, the effect of inclined tensile steel reinforcement, and the compression chord influence. The verification of the proposed formula has been conducted on the experimental test results of 26 non-prismatic beams with or without openings at the same loading conditions. The results reflect that the predicted formula finds the shear capacity of non-prismatic beams with openings, it is co

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Publication Date
Sun Jun 11 2017
Journal Name
Al-academy
Performance difficulties of Sharif Muhiyddin Haider’s musical works among Oud students
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This research focuses on the difficulties that face Oud's students' in the performance of Sharif Muheyddin Haider musical works. In addition, this research suggests solutions to overcome these difficulties for make it easier to play Haider's musical works. This research also addressed important topics of great relevance the title, problem and the research's aims. Moreover, Procedures of this research adopted the descriptive approach (content analysis) to attain the research's aims. Furthermore, results and discussions where covered, and conclusions of the appropriate academic solutions were achieved to overcome the performance difficulties of Haider's musical works among Oud's students'. At the end, the research presents a set of recomme

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Publication Date
Sun Dec 01 2019
Journal Name
Journal Of Economics And Administrative Sciences
Using Markov chains to forecast the exports of Iraqi crude oil
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       In this paper, the topic of forecasting the changes in the value of Iraqi crude oil exports for the period from 2019 to 2025, using the Markov transitional series based on the data of the time series for the period from January 2011 to November 2018, is real data obtained from the published data of the Central Agency Of the Iraqi statistics and the Iraqi Ministry of Oil that the results reached indicate stability in the value of crude oil exports according to the data analyzed and listed in the annex to the research.

Keywords: Using Markov chains

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Crossref
Publication Date
Tue Dec 21 2021
Journal Name
Journal Of Engineering Mathematics
Fluid inflow from a source on the base of a channel
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