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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 Jun 30 2023
Journal Name
حوليات اداب عين شمس
Names of Day of Resurrection in the Hebrew translation of the meanings of the Holy Quran An analytical study Uri Rubin translation as a model
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The present study discusses the names of the Day of Resurrection in Uri Rubin’s translations of the Holy Qur’an. To identify the translation difficulties and complications and to find out the Hebrew equivalence, the study, through the application of a comparative analytical approach, aims at analyzing the linguistic structures of Day of Resurrection names cited in the Holy Qur’an. Heavenly religions are rich with distinct and unique terms that distinguish and reflect their specificity of other religions; something requires a great accuracy in the translation of such terminology. By investigating selected examples of the names of the Day of Resurrection in Arabic and Hebrew, the present study sheds light on the morphological and semant

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Publication Date
Tue Sep 08 2020
Journal Name
Baghdad Science Journal
Evaluation of Different Nitrogen Management on Yield and Some of the Yield Components of Rice (Shiroudi cultivar)
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Nitrogen (N) is a key growth and yield-limiting factor in cultivated rice areas. This study has been conducted to evaluate the effects of different conditions of N application on rice yield and yield components (Shiroudi cultivar) in Babol (Mazandaran, Iran) during the 2015- 2016 season. A factorial experiment executed of a Randomized Complete Block Design (RCBD) used in three iterations. In the first factor, treatments were four N amounts (including 50, 90, 130, and 170 kg N ha-1), while in the second factor, the treatments consisted of four different fertilizer splitting methods, including T1:70 % at the basal stage + 30 % at the maximum tillering stage, T2:1/3 at the basal stage + 1/3 at the maximum ti

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Publication Date
Sun Jan 19 2020
Journal Name
Biochemical And Cellular Archives
Isolation and characterization of phosphate solubilizing Pseudomonas species and assess its efficacy as plant growth promoter
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Scopus
Publication Date
Tue Oct 01 2024
Journal Name
Journal Of Engineering Science And Technology
NUMERICAL SIMULATION OF SHEET PILES AS A SEEPAGE CUTTER OFF: AL-KIFIL REGULATOR AS A CASE STUDY
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Sheet piles are necessary with hydraulic structures as seepage cut-off to reduce the seepage. In this research, the computational work methodology was followed by building a numerical model using Geo-Studio program to check the efficiency of using concrete sheet piles as a cut-off or reducer for seepage with time if the sheet piles facing the drawdown technique. Al-Kifil regulator was chosen as a case study, an accurate model was built with a help of observed reading of the measuring devices, which was satisfactory and helped in checking the sheet piles efficiency. Through the study, three scenarios were adopted (with and without) drawdown technique, it was found that at the short time there's no effect of the drawdown technique on

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Scopus
Publication Date
Fri Jul 21 2023
Journal Name
Journal Of Engineering
Performance Evaluation and Comparison Between LDPC and Turbo Coded MC-CDMA
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This work presents a comparison between the Convolutional Encoding CE, Parallel Turbo code and Low density Parity Check (LDPC) coding schemes with a MultiUser Single Output MUSO Multi-Carrier Code Division Multiple Access (MC-CDMA) system over multipath fading channels. The decoding technique used in the simulation was iterative decoding since it gives maximum efficiency at higher iterations. Modulation schemes used is Quadrature Amplitude Modulation QAM. An 8 pilot carrier were
used to compensate channel effect with Least Square Estimation method. The channel model used is Long Term Evolution (LTE) channel with Technical Specification TS 25.101v2.10 and 5 MHz bandwidth bandwidth including the channels of indoor to outdoor/ pedestrian

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Publication Date
Wed Oct 26 2022
Journal Name
Iraqi Journal Of Science
Gene Expression Analysis via Spatial Clustering and Evaluation Indexing
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The density-based spatial clustering for applications with noise (DBSCAN) is one of the most popular applications of clustering in data mining, and it is used to identify useful patterns and interesting distributions in the underlying data. Aggregation methods for classifying nonlinear aggregated data. In particular, DNA methylations, gene expression. That show the differentially skewed by distance sites and grouped nonlinearly by cancer daisies and the change Situations for gene excretion on it. Under these conditions, DBSCAN is expected to have a desirable clustering feature i that can be used to show the results of the changes. This research reviews the DBSCAN and compares its performance with other algorithms, such as the tradit

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Publication Date
Mon Jan 01 2024
Journal Name
Aip Conference Proceedings
Negative skin friction evaluation and mitigation: A review study
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Publication Date
Tue Jun 30 2020
Journal Name
Journal Of Economics And Administrative Sciences
Compare Prediction by Autoregressive Integrated Moving Average Model from first order with Exponential Weighted Moving Average
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The prediction process of time series for some time-related phenomena, in particular, the autoregressive integrated moving average(ARIMA) models is one of the important topics in the theory of time series analysis in the applied statistics. Perhaps its importance lies in the basic stages in analyzing of the structure or modeling and the conditions that must be provided in the stochastic process. This paper deals with two methods of predicting the first was a special case of autoregressive integrated moving average which is ARIMA (0,1,1) if the value of the parameter equal to zero, then it is called Random Walk model, the second was the exponential weighted moving average (EWMA). It was implemented in the data of the monthly traff

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Publication Date
Sat Apr 16 2022
Journal Name
Pakistan Journal Of Medical And Health Science
Evaluation the Efficacy of Bacteriophage Against Pseudomonas Aeruginosa Isolated from Wound and Burn Infections
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Publication Date
Fri Dec 15 2023
Journal Name
Iraqi Journal Of Laser
Evaluation of Lithium Disilicate Surface Morphology Treated with Er,Cr:YSGG and Fractional CO2 Laser
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Abstract: The use of indirect, all-ceramic restorations has grown in popularity among dentists. Studies have demonstrated that for indirect ceramic restorations to be effective over time, cement and ceramic must be bonded in a stable manner. Chemical, mechanical, and laser irradiation are among the methods used to precondition ceramic surfaces in order to increase bond strength.The objective of the study: This study was performed to investigate the roughness values and surface topography of lithium disilicate glass-ceramic treated with conventional methods and different Er,Cr:YSGG, and fractional CO2 laser conditioning parameters.Material and methods:<

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