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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
Sat Oct 28 2023
Journal Name
Baghdad Science Journal
Numerical Modeling of Renal Ionic Equilibrium for Implantable Kidney Applications
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The human kidney is one of the most important organs in the human body; it performs many functions
and has a great impact on the work of the rest of the organs. Among the most important possible treatments is
dialysis, which works as an external artificial kidney, and several studies have worked to enhance the
mechanism of dialysate flow and improve the permeability of its membrane. This study introduces a new
numerical model based on previous research discussing the variations in the concentrations of sodium,
potassium, and urea in the extracellular area in the blood during hemodialysis. We simulated the differential
equations related to mass transfer diffusion and we developed the model in MATLAB Simu

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Publication Date
Tue May 01 2018
Journal Name
Journal Of Physics: Conference Series
Photoluminescence Spectra From The Direct Energy Gap of a-SiQDs
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Publication Date
Wed Apr 01 2020
Journal Name
Plant Archive
Genetic analysis of sorghum cultivars from USA using SSR markers
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Publication Date
Wed Jan 01 2014
Journal Name
Journal Of Engineering
Punching Shear Strength of Reinforced Concrete Flat Plates with Openings
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Publication Date
Mon Jun 01 2020
Journal Name
International Journal Of Electrical And Computer Engineering (ijece)
Thermal response of skin diseased tissue treated by plasmonic nanoantenna
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The thermal distribution in the diseased tissue treated by different methods faces the problem of an uncontrollable defused heat. In the present article, we use a plasmonic bowtie nanoantenna working in the near infrared region to enhance the temperature confinement in the tissue. The Computer Simulation Technology Studio Suite package version 2019 was used to execute the design of both plasmonic nanoantenna and the tissue. Gold nanostructure and silicon carbide dioxide are the components the plasmonic nanoantenna in the bowtie shape. The results showed that the distance between the tumor tissue and the antenna is important to determine the intensity field where the maximum field is 5.9*107 V/m at a distance of 100 nm. The maximum

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Crossref (7)
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Publication Date
Mon Feb 18 2019
Journal Name
Iraqi Journal Of Physics
Elastic transverse electron scattering form factors of 11Li exotic nucleus
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        The elastic transverse electron scattering form factors have been studied for the 11Li   nucleus using the Two- Frequency Shell Model (TFSM) approach. The single-particle wave functions of harmonic-oscillator (HO) potential are used with two different oscillator parameters bcore and bhalo. According to this model, the core nucleons of 9Li nucleus are assumed to move in the model space of spsdpf. The outer halo (2-neutron) in 11Li is assumed to move in the pure 1p1/2, 1d5/2, 2s1/2 orbit. The shell model calculations are carried ou

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Publication Date
Thu Mar 01 2018
Journal Name
Journal Of Engineering
Flexible Genetic Algorithm Based Optimal Power Flow of Power Systems
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Nowadays, the power plant is changing the power industry from a centralized and vertically integrated form into regional, competitive and functionally separate units. This is done with the future aims of increasing efficiency by better management and better employment of existing equipment and lower price of electricity to all types of customers while retaining a reliable system. This research is aimed to solve the optimal power flow (OPF) problem. The OPF is used to minimize the total generations fuel cost function. Optimal power flow may be single objective or multi objective function. In this thesis, an attempt is made to minimize the objective function with keeping the voltages magnitudes of all load buses, real outp

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Crossref
Publication Date
Sat Feb 09 2019
Journal Name
Iraqi Journal Of Laser
Treatment of Oral Pyogenic Granuloma by 810 nm Diode Laser
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Pyogenic granuloma is one of the inflammatory hyperplasia seen in the oral cavity. The
present study included 10 patients with pyogenic granuloma, involving 4 males and 6 females with 1:1.5
male to female ratio. Patient ages ranged from 5 to 85 years (mean, 30 years) and half of the lesions had
pedunculated base, with surface ulceration in 10% of cases. Treatment consisted of resection, using 810
nm diode lasers. Eight patients were anesthetized during the surgical operation by local infiltration of
anesthesia. Only three patients reported mild post-operative pain within the first 24 hours of the healing
period. During the surgical operation there was no significant bleeding so clear surgical field. There was
no blee

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Publication Date
Tue Dec 16 2008
Journal Name
Iraqi Journal Of Laser
Treatment of Oral Pyogenic Granuloma by 810 nm Diode Laser
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Pyogenic granuloma is one of the inflammatory hyperplasia seen in the oral cavity. The
present study included 10 patients with pyogenic granuloma, involving 4 males and 6 females with 1:1.5
male to female ratio. Patient ages ranged from 5 to 85 years (mean, 30 years) and half of the lesions had
pedunculated base, with surface ulceration in 10% of cases. Treatment consisted of resection, using 810
nm diode lasers. Eight patients were anesthetized during the surgical operation by local infiltration of
anesthesia. Only three patients reported mild post-operative pain within the first 24 hours of the healing
period. During the surgical operation there was no significant bleeding so clear surgical field. There was
no blee

... Show More
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Publication Date
Thu Dec 01 2016
Journal Name
Journal Of Cleaner Production
A study of biogas production from date palm fruit wastes
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