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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 Mar 15 2019
Journal Name
Al-khwarizmi Engineering Journal
Desalination of Highly Saline Water Using Direct Contact Membrane Distillation (DCMD)
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In this work, laboratory experiments were carried out to verify direct contact membrane distillation system’s performance in highly saline water desalination. The study included the investigation of various operating conditions, like feed flow rate, temperature and concentration of NaCl solution and their impact on the permeation flux were discussed. 16 cm2 of a flat sheet membrane module with commercial poly-tetra-fluoroethylene (PTFE) membrane, which has 0.22 μm pore size, 96 µm thickness and 78% average porosity, was used. A high salt rejection factor was obtained greater than 99.9%, and the permeation flux up to 17.27 kg/m2.h was achieved at 65°C for hot feed side and 20°C for cold side stream.

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Publication Date
Thu Aug 01 2019
Journal Name
Iop Conference Series: Materials Science And Engineering
Effect of Embedment Depth on Raft Foundation Settlement Under Seismic Load
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Abstract<p>Dynamic loads highly influence soil properties and may cause real damage to structures and buildings. This article reports the experimental results from 24 tests to study the settlement of flexible and rigid raft foundation with different embedment depth rested on dense sandy soil. A small scale building model of dimension 200*200 mm and 320 mm in height was performed with reinforced concrete raft foundation of 10 mm thickness for flexible raft and 23 mm for rigid raft, The shaking table technique was used to simulate the seismic effect, the shaker was sat to give three different excitation frequencies 1,2,and3 Hz and displacement amplitude equal to 13 mm, the foundation was placed at</p> ... Show More
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Publication Date
Tue Oct 01 2024
Journal Name
Journal Of Ecological Engineering
Treatment of Petroleum Refinery Wastewater by Activated Carbon Assisted Electrocoagulation Process
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The removal of COD from wastewater generated by petroleum refinery has been investigated by adopting electrocoagulation (EC) combined with adsorption using activated carbon (AC) derived from avocado seeds. The process variables influencing COD removal were studied: current density (2–10 mA/cm2), pH (4–9), and AC dosage (0.2–1 g/L). Response surface methodology (RSM) based on Box–Behnken design (BBD) was used to construct a mathematical model of the EC/AC process. Results showed that current density has the major effect on the COD removal with a percent of contribution 32.78% followed by pH while AC dosage has not a remarkable effect due to the good characteristics of AC derived from avocado seeds. Increasing current density gives be

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Publication Date
Mon Nov 09 2020
Journal Name
Journal Of The Optical Society Of America B
Theoretical study of silicon-based Bragg mirrors for cavity QED applications
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We conducted a theoretical study on the potential use of amorphous hydrogenated silicon (a-Si:H) as the high-index material in quarter-wave-stack Bragg mirrors for cavity quantum electrodynamics applications. Compared to conventionally employed T a 2

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Publication Date
Mon Jun 01 2020
Journal Name
Case Studies In Thermal Engineering
Al2O3-water nanofluid heat transfer enhancement of a twin impingement jet
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Publication Date
Tue Aug 16 2016
Journal Name
International Journal Of Computer Applications
Experimental Study of CLARK-Y Smoothed Inverted Wing with Ground Effect
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Publication Date
Fri Feb 10 2023
Journal Name
Journal Of Applied Mathematics
The Dynamics of a Delayed Ecoepidemiological Model with Nonlinear Incidence Rate
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In this paper, the general framework for calculating the stability of equilibria, Hopf bifurcation of a delayed prey-predator system with an SI type of disease in the prey population, is investigated. The impact of the incubation period delay on disease transmission utilizing a nonlinear incidence rate was taken into account. For the purpose of explaining the predation process, a modified Holling type II functional response was used. First, the existence, uniform boundedness, and positivity of the solutions of the considered model system, along with the behavior of equilibria and the existence of Hopf bifurcation, are studied. The critical values of the delay parameter for which stability switches and the nature of the Hopf bifurcat

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Publication Date
Mon Apr 30 2018
Journal Name
Journal Of Materials Science: Materials In Electronics
H2S gas sensitivity of PAni nano fibers synthesized by hydrothermal method
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In this work, PAni nanofibers (NFs) are successfully synthesized via hydrothermal method. The structural, surface morphological, optical, electrical and H2S gas sensing properties have been investigated for PAni thin films deposited by spin coating technique. The XRD pattern reveals crystalline nature of PAni NFs with crystallite size of 9.2 nm. The SEM image of Polyaniline clearly indicates that the polymer possesses nanofiber like structure. The optical properties show that the optical energy gap follows allowed direct electronic transition calculated using Tauc’s equation. Intense hotoluminescence (PL) peaks at 309, 340 and 605 nm are observed. The electrical properties such as D.C. conductivity and Hall effect have been studied wher

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Publication Date
Wed Dec 13 2017
Journal Name
Al-khwarizmi Engineering Journal
Improving Shear Strength of Soft Clay by Using Torn Belts Chips
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Random throwing of industrial waste has a significant impact on the environment unless it takes into account the conditions of engineered destroying and/or re-used. Taking the advantage of re-using waste materials in engineering projects represents a well-planned project in order to resolve a lot of engineering problems for some difficult soils. The objective of this study was to evaluate the capability and effects of Rubber Shreds (RS) from scrap torn belts towards improving the shear strength of soft clay. A direct shear tests were conducted on soft clay-RS mixture. The following parameters were investigated to study the influence of RS content, water content, normal stress, and dilation ratio. From experimental test results it was fou

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Publication Date
Fri Jul 01 2011
Journal Name
Bulletin Of The Iraq Natural History Museum (p-issn: 1017-8678 , E-issn: 2311-9799)
A NEW SPECIES OF RHYNCOMYAROB.-DESVOIDY, 1830 (DIPTERA : CALLIPHORIDAE) FROM IRAQ
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This research includes a detaile description of new species Rhyncomya irakensis sp. nov.
from Iraq.
Localities distribution, host plants and data of collection were recorded.

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