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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
Thu Jul 20 2023
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
Synthesis and Characterization Graphene- Carbon Nitride Nanostructure in One Step
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Graphene-carbon nitride can be synthesized from thiourea in a single step at a temperature of four hours at a rate of 2.3 ℃/min. Graphene-carbon nitride was characterized by Fourier-transform infrared spectroscopy (FTIR), energy dispersive X-ray analysis (EDX), scanning electron microscopy, and spectrophotometry (UV-VIS). Graphene-carbon nitride was found to consist of triazine and heptazine structures, carbon, and nitrogen. The weight percentage of carbon and the atomic percentage of carbon are 40.08%, and the weight percentage of nitrogen and the atomic percentage of nitrogen are 40.08%. Therefore, the ratio and the dimensions of the graphene-carbon nitride were characterized by scanning electron microscopy, and it was found that the

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Publication Date
Sun Dec 25 2022
Journal Name
International Journal Of Drug Delivery Technology
Effect of Zinc drug on amino acid concentration in liver of white mice, Mus musculus
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Zinc is one of the essential trace elements, it plays a key role in many biochemical and functional processes. It is less harmful than many other minerals, in the case of exposure to high doses of zinc, poisoning occurs, and this poisoning may mostly result from the accidental ingestion of household products containing zinc or nutritional supplements, this study was conducted to find out the effects of zinc on the concentration of amino acid. A total of 30 adult white mouse males were taken and divided into three groups; the first group (control) of 10 mice taken with distilled water for 30 days, the second group includes 10 mice that were dose with Zn drug concentration of 50 mg/kg/day for 30 days, the third group includes 10 mice that wer

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Publication Date
Sat Jan 01 2022
Journal Name
Journal Of International Society Of Preventive And Community Dentistry
Investigating tensile bonding and other properties of yttrium oxide nanoparticles impregnated heat-cured soft-denture lining composite in vitro
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Aims: This study was conducted to assess the effect of the addition of yttrium oxide (Y2O3) nanoparticles on the tensile bond strength, tear strength, shore A hardness, and surface roughness of soft-denture lining material. Materials and Methods: Y2O3 NPs with 1.5 and 2 wt.% were added into acrylic-based heat-cured soft-denture liner. A total of 120 specimens were prepared and divided into four groups according to the test to be performed (tensile bond strength, tear strength, surface hardness, and surface roughness). Results: There was a highly significant increase in tensile bond strength between the soft liner and the acrylic denture base, tear strength, and hardness at both concentrations as compared to the control group, whereas ther

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Publication Date
Thu Mar 15 2018
Journal Name
Journal Of Baghdad College Of Dentistry
In vitro Performance of Polymethyl–methacrylate with Ultra High Density Poly Ethylene Fiber and Nano Zirconium Oxide Particles Composite
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Background: Poly (methyl methacrylate) has been widely utilized for fabrication of dentures for many years as it has good advantages but not achieved all demands of the mechanical properties such as low transverse strength, low impact strength, low surface hardness, high water solubility and high water sorption. Material and method: To provide bonding between ZrO2 nanoparticles and PMMA matrix, the ZrO2 Nano-fillers were surface-treated with a saline coupling agent. Plasma surface treatment of polyethylene (PE) fiber was done to change surface fiber by using DC- glow discharge system. For characterization of interring any functional groups, the (FTIR) spectrum were done .then the mechanical properties studied to choose the appropriate perc

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Publication Date
Sun Dec 01 2019
Journal Name
Baghdad Science Journal
Comparison between Biological Activities of Commercial and Synthesized Carbon Nanotubes by Flame Fragments Deposition Technique
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Carbon nanotubes (CNTs) were synthesized via liquefied petroleum gas (LPG) as precursor using flame fragments deposition (FFD) technique. In vitro, biological activates of carbon nanotubes (CNTs) synthesized by FFD technique were investigated. The physiochemical characterizations of synthesized CNTs are similar to other synthesized CNTs and to the standard sample. Pharmaceutical application of synthesized CNTs was studied via conjugation and adsorption with different types of medicines as promote groups. The conjugation of CNTs was performed by adsorption the drugs such as sulfamethoxazole (SMX) and trimethoprim (TMP) on CNTs depending on physical properties of both bonded parts. The synthesized CNTs almost have the same performance in a

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Publication Date
Sat Dec 30 2023
Journal Name
Iraqi Journal Of Science
An Overview of General Regulations to Minimize Environmental Affects from Petroleum Drilling and Production Activities
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Improved environmental protection requires better education and training of regulations which manage different available activities in petroleum operations.
Data from industry is very important to ensure that the existing or suggested regulations are based on accurate scientific information and that they contribute to best environmental protection without adding useless restrictions to this industry.
This research deals with an overview of major environmental regulations and issues facing the petroleum industry.
Many issues which regulate drilling and production activities that may pollute surface water, clean up of existing hazardous waste sites, storage and management of various chemicals and other important aspects are listed

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Publication Date
Fri Feb 08 2019
Journal Name
Iraqi Journal Of Laser
Sealing Depth of Q-Switched Nd:YAG 1064nm Laser in the Treatment of Patients with Hypersensitive Teeth: An In Vitro Study
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The purpose of this work was to study the effects of the Nd:YAG laser on exposed dentinal
tubules of human extracted teeth using a scanning electron microscope (SEM). Eighty 2.5mm-thick
slices were cut at the cementoenamel junction from 20 extracted human teeth with an electric saw. A
diamond bur was used to remove the cementum layer to expose the dentinal tubules. Each slice was
sectioned into four equal quadrants and the specimens were randomly divided into four groups (A to D ).
Groups B to D were lased for 2 mins using an Nd:YAG laser at 6 pulses per second at energy outputs of
80 , 100 and 120 mJ. Group A served as control. Under SEM observation, nonlased specimens showed
numerous exposed dentinal tubules. SEM o

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Publication Date
Sun Nov 26 2017
Journal Name
Journal Of Engineering
Compression Index and Compression Ratio Prediction by Artificial Neural Networks
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Information about soil consolidation is essential in geotechnical design. Because of the time and expense involved in performing consolidation tests, equations are required to estimate compression index from soil index properties. Although many empirical equations concerning soil properties have been proposed, such equations may not be appropriate for local situations. The aim of this study is to investigate the consolidation and physical properties of the cohesive soil. Artificial Neural Network (ANN) has been adapted in this investigation to predict the compression index and compression ratio using basic index properties. One hundred and ninety five consolidation results for soils tested at different construction sites

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Publication Date
Sat Jan 01 2022
Journal Name
Dental Hypotheses
Comparison of Microleakage of Composite and Glass Ionomer Restorations in Primary Molars Pretreated with Silver Diamine Fluoride at Two Time Intervals: An In Vitro study
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Publication Date
Sat May 02 2015
Journal Name
Advances In Life Science And Technology
Cytotoxic Effect of Aqueous Extract of Anastatica hierochuntica L. on AMN-3 Cell Line in vitro
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Anastatica hierochuntica L. is distributed throughout Arabain Peninsula, and elsewhere it is locally called "Kuffe Maryam" .All parts of the plant are used in folk medicine. This study amid to investigate the effect of aqueous extract of anastatica hierochunctica L. on the cancer cell lines AMN-3. Anti cancer activity of aqueous extract of anastatica hierochunctica L. showed anticancer activity against AMN-3 cell line for twelve concentrations (0.04, 0.09, 0.195, 0.39, 0.78, 1.56, 3.125, 6.25, 12.5, 25, 50, 100) mg/mL in comparison with negative control.