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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
Sun Jul 01 2018
Journal Name
Agronomy Journal
Use of Rainfall Data to Improve Ground-Based Active Optical Sensors Yield Estimates
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Ground-based active optical sensors (GBAOS) have been successfully used in agriculture to predict crop yield potential (YP) early in the season and to improvise N rates for optimal crop yield. However, the models were found weak or inconsistent due to environmental variation especially rainfall. The objectives of the study were to evaluate if GBAOS could predict YP across multiple locations, soil types, cultivation systems, and rainfall differences. This study was carried from 2011 to 2013 on corn (Zea mays L.) in North Dakota, and in 2017 in potatoes in Maine. Six N rates were used on 50 sites in North Dakota and 12 N rates on two sites, one dryland and one irrigated, in Maine. Two active GBAOS used for this study were GreenSeeker and Holl

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Publication Date
Thu Dec 12 2013
Journal Name
Iraqi Journal Of Science
Determination of Optimum Mechanical Drilling Parameters for an Iraqi Field with Regression Model
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Publication Date
Sat Jan 01 2022
Journal Name
The Iraqi Postgraduate Medical Journal
Augmentation of depressed nasal dorsum by diced cartilage graft wrapped with fascia lata
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BACKGROUND: Dorsal reconstruction and augmentation for a saddle nose or generalized under projecting nose (familial ) require some type of grafting that increase the volume, raise the radix , raise the entire dorsum ,camouflage the osseocartilaginous junction or any irregularity along the dorsum, diced cartilage graft wrapped with fascia lata used to achieve that . AIM OF THE STUDY : The purpose of the study was to assess the aesthetic and functional outcome of dorsal augmentation by diced cartilage graft wrapped with fascia lata. PATIENTS AND METHODS: Between July 2018 and May 2019. 7 patients included ,4 females and 3 males ,their age ranged between 20 to 37 years ,5 were primary and 2 secondary case rhinoplasty,2 operated by closed appro

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Publication Date
Sun Mar 30 2014
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Optimization of Activated Carbon Preparation from Date Stones by Microwave Assisted K2CO3 Activation
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The preparation of activated carbon (AC) from date stones by using microwave assisted K2CO3 activation was investigated in this paper. The influence of radiation time, radiation power, and impregnation ratio on the yield and methylene blue (MB) uptake of such carbon were studied. Based on Box-Wilson central composite design, two second order polynomial models were developed to correlate the process variables to the two responses. From the analysis of variance the significant variables on each response were identified. Optimum coditions of 8 min radiation time, 660 W radiation power and 1.5 g/g impregnation ratio gave 460.123 mg/g MB uptake and 19.99 % yield. The characteristics of the AC were examined by pore structure analysis, and scan

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Publication Date
Sat Jan 01 2011
Journal Name
College Of Engineering Journal
Study the Effect of Cutting Conditions for turning process on the Machined Surface
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Surfaces quality is one of the most specified customer requirements for machine parts. The major indication of surfaces quality on machined parts is surface roughness. The research aim is to study the cutting conditions and their effects on the surface roughness. This paper utilizes regression models to predict surface roughness over the machining time for variety of cutting conditions in turning. In the experimental part for turning, different types of materials (Aluminum alloy, Copper alloy, and Gray cast iron) were considered with different cutting speed ( ) and feed rate ( ). A mathematical Model depending on statistical-mathematical method between surface roughness (Rz ) and cutting condition ( , ) were derived, for the three materials

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Publication Date
Sat Aug 31 2024
Journal Name
International Review On Modelling And Simulations (iremos)
Thermal Buckling Analysis of Composite Laminated Shells Using Higher Order Shear Deformation Theory
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Publication Date
Sat Jul 20 2024
Journal Name
Sumer Journal For Pure Science
Classify the Nutritional Status of Iraqi children under Five Years Using Fuzzy Classification
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Publication Date
Thu Mar 02 2023
Journal Name
Iar Journal Of Business Management
Reducing The Costs Of Transporting Multiple Products (Linear Transport Problems) Using Excel QM
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The transportation model is a well-recognized and applied algorithm in the distribution of products of logistics operations in enterprises. Multiple forms of solution are algorithmic and technological, which are applied to determine the optimal allocation of one type of product. In this research, the general formulation of the transport model by means of linear programming, where the optimal solution is integrated for different types of related products, and through a digital, dynamic, easy illustration Develops understanding of the Computer in Excel QM program. When choosing, the implementation of the form in the organization is provided.

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Publication Date
Fri Feb 01 2019
Journal Name
Journal Of Physics: Conference Series
Study the Electronic Properties of Boron Nitride Diamondiod Nanostructure using Ab-initio DFT
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Publication Date
Fri Jan 01 2021
Journal Name
Journal Of Engineering
Design of a PID-Lead Compensator for a Twin Rotor Aerodynamic System (TRAS)
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This paper deals with a Twin Rotor Aerodynamic System (TRAS). It is a Multi-Input Multi-Output (MIMO) system with high crosscoupling between its two channels. It proposes a hybrid design procedure that combines frequency response and root locus approaches. The proposed controller is designated as PID-Lead Compensator (PIDLC); the PID controller was designed in previous work using frequency response design specifications, while the lead compensator is proposed in this paper and is designed using the root locus method. A general explicit formula for angle computations in any of the four quadrants is also given. The lead compensator is designed by shifting the dominant closed-loop poles slightly to the left in the s-plane. This has the effect

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