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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
Mon Feb 18 2019
Journal Name
Iraqi Journal Of Physics
BVR CCD Photometric observation analysis of spiral galaxy Ic 467
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The structure and composition of the stellar population in the surface brightness galaxy Ic 467 is studied using BVR CCD photometry. The observations were obtained on the 1.88m optical telescope of Kottamia Astronomical Observatory, KAO, Egypt. A two-dimensional decomposition of the galaxy bulge and disk components is carried out. A powerful star forming region is observed near the galactic center. Based on the positions of the various components of the galaxy in two color diagrams and the surface brightness of the eastern arms in V filter is brighter than the western arm. From the observations, the surface brightness profiles, Ellipticity profiles, position angle profiles and color indices profiles are described and studied.

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Publication Date
Wed Oct 02 2013
Journal Name
Journal Of Biology, Agriculture And Healthcare
The Prevalence of Aerobic Bacteria Isolated from Horses Fecal Samples
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Dietary components and changes cause shifts in the gastrointestinal microbial ecology that can play a role in animal health and a wide range of diseases. However, most information about the microbial populations in the gut of horses has not been quantitative. The objective of this study was to characterize the fecal bacterial and its prevalence in healthy horses and diarrheal one in a period from September 2010 to July 2013. Out of 100 Fecal samples of horses (from farms in Al-furusyia club) in Baghdad were examined for microbial differentiation founded eighty percent of the fecal samples isolated from healthy horses. The most common pathogen found were Streptococcus spp. (33.7%), Escherichia coli (20.9%), , and Staphylococcus aureus (9.2

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Publication Date
Sun Jan 01 2023
Journal Name
Aip Conference Proceedings
Osmotically assisted reverse osmosis (OARO) for desalination of brackish water
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Publication Date
Sun Apr 30 2017
Journal Name
Ibn Al-haitham Journal For Pure And Applied Science
Evidence Supports The Formation Of Isoimides Derived From Pyromellitic Dianhydride
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Some new mono isoimides of asymmetrical pyromillitdiimide derived from pyromellitic dianhydride were synthesized and studied by their melting points, FTIR, and 1HNMR spectroscopy and CHN analysis (for some of them) and it was proved that the mechanism of the formation of these isoimides followed, the mechanism suggested by Cotter et al. by using N, N─-dicyclohexylcarbodiimide as dehydrating agent, in spite of the groups attached to the phenyl moiety as mentioned in literatures.

Publication Date
Thu Mar 30 2023
Journal Name
Journal Of Economics And Administrative Sciences
Comparison of Some Methods for Estimating Nonparametric Binary Logistic Regression
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In this research, the methods of Kernel estimator (nonparametric density estimator) were relied upon in estimating the two-response logistic regression, where the comparison was used between the method of Nadaraya-Watson and the method of Local Scoring algorithm, and optimal Smoothing parameter λ was estimated by the methods of Cross-validation and generalized Cross-validation, bandwidth optimal λ has a clear effect in the estimation process. It also has a key role in smoothing the curve as it approaches the real curve, and the goal of using the Kernel estimator is to modify the observations so that we can obtain estimators with characteristics close to the properties of real parameters, and based on medical data for patients with chro

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Crossref
Publication Date
Wed Sep 24 2025
Journal Name
Dijlah Journal Of Medical Sciences P-issn:3078-3178, E-issn:3078-8625
pdf Review Article Biochemical Impact of Trace Elements on Metabolism
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Numerous trace elements, notably metals, are essential for the normal functioning of several biological reactions, especially as enzyme cofactors. Several Trace elements refer to essential micronutrients required in minimal quantities for certain biological functions pertaining to human metabolism, albeit their minimal concentrations in the organism. Nonetheless, our understanding of this topic is considerably restricted, and emerging insights into their metabolic functions necessitate contributions and have implications across various domains, encompassing nutritional chemistry, with a focus on analytical chemistry, biological sciences, medicine, pharmacology, and agricultural sciences. 

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Crossref
Publication Date
Thu Oct 01 2015
Journal Name
International Journal Of Engineering And Advanced Technology (ijeat)
Optimization Process Parameters of Submerged Arc Welding Using Taguchi Method
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Submerged arc welding (SAW) process is an essential metal joining processes in industry. The quality of weld is a very important working aspect for the manufacturing and construction industries, the challenges are made optimal process environment. Design of experimental using Taguchi method (L9 orthogonal array (OA)) considering three SAW parameter are (welding current, arc voltage and welding speed) and three levels (300-350-400 Amp. , 32-36-40 V and 26-28-30 cm/min). The study was done on SAW process parameters on the mechanical properties of steel type comply with (ASTM A516 grade 70). Signal to Noise ratio (S/N) was computed to calculate the optimal process parameters. Percentage contributions of each parameter are validated by using an

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Publication Date
Fri Jul 01 2016
Journal Name
International Journal Of Computer Science And Mobile Computing
Hybrid Color Image Compression of Hard & Soft Mixed Thresholding Techniques
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Publication Date
Sat Nov 01 2014
Journal Name
Journal Of Engineering
Saponification of Diethyl Adipate with Sodium Hydroxide Using Reactive Distillation
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This research presents a new study in reactive distillation by adopting a consecutive reaction . The adopted consecutive reaction was the saponification reaction of diethyl adipate with NaOH solution. The saponification reaction occurs in two steps. The distillation process had the role of withdrawing the intermediate product i.e. monoethyl adipate from the reacting mixture before the second conversion to disodium adipate occurred. It was found that monoethyl adipate appeared successfully in the distillate liquid. The percentage conversion from di-ester to monoester was greatly enhanced (reaching 86%) relative to only 15.3% for the case of reaction without distillation .This means 5 times enhancement . The presence of two layers in both the

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Publication Date
Sun Jan 01 2017
Journal Name
International Journal Of Chem Tech Research
theoretical study to calculate some parameters of ion optical system
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