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New Niflumic Acid Derivatives as EGFR Inhibitors: Design, Synthesis, In silico Studies, and Anti-proliferative Assessment
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Background:

1,3,4-oxadizole and pyrazole derivatives are very important scaffolds for medicinal chemistry. A literature survey revealed that they possess a wide spectrum of biological activities including anti-inflammatory and antitumor effects.

Objectives:

To describe the synthesis and evaluation of two classes of new niflumic acid (NF) derivatives, the 1,3,4-oxadizole derivatives (compounds 3 and (4A-E) and pyrazole derivatives (compounds 5 and 6), as EGFR tyrosine kinase inhibitors in silico and in vitro.

Methods:

The designed compounds were synthesized using conventional organic synthesis methods. The antitumor activities of the new NF derivatives against HepG2 hepatocellular carcinoma and A549 non-small cell lung cancer cell lines were assessed in vitro via MTT assay, flow cytometry, RT-PCR, as well as via molecular docking studies.

Results:

The cytotoxicity results indicated that the newly synthesized NF derivatives were cytotoxic against the two cancer cell lines, with compound 6 being the most cytotoxic, achieving the lowest IC50 concentration. Furthermore, compound 6 targeted EGFR tyrosine kinase leading to cell cycle arrest at the G2/M cell cycle phase and induction of apoptosis. The in vitro biological investigation results matched those of the molecular docking analysis. In conclusion, the new NF derivatives, specifically compound 6, exhibited favorable pharmacokinetic features and are promising EGFR tyrosine kinase inhibitors.

Conclusion:

A series of niflumic acid derivatives (3, 4A-E, 5, and 6) were successfully created, and FT-IR, 1H, 13CNMR, and HRMS were used to confirm their chemical structures. According to molecular docking studies, compounds 3, 5, and 6 have the highest docking scores (ΔG), and most tested compounds have a good pharmacokinetic profile. Results of compound 6 in vitro antitumor activities showed that it is a promising EGFR tyrosine kinase inhibitor.

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Publication Date
Mon Jan 08 2024
Journal Name
Al-academy
Evaluation of subject curriculum vocabulary Fundamentals of design from the point of view of its teachers
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The curriculum is a tool of the basic tools that seek through which educational institutions to achieve the objectives of any educational policy, and therefore must be a practical application of curriculum objectives of this policy. If, however, described the separate curricula for educational policy, that would be evidence of planning that leads to failure in achieving the great goals of society. The curriculum does not include the subject of education only, but goes to all the educational experiences that achieve the desired behavioral goals.
When goal-setting study for any of the articles should study the use of the overall goals of the article. And therefore must serve the general goals of academic material and objectives in one d

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Publication Date
Thu Jan 01 2015
Journal Name
Journal Of Engineering
A Visual Interface Design for Evaluating the Quality of Google Map Data for some Engineering Applications
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Today, there are large amounts of geospatial data available on the web such as Google Map (GM), OpenStreetMap (OSM), Flickr service, Wikimapia and others. All of these services called open source geospatial data. Geospatial data from different sources often has variable accuracy due to different data collection methods; therefore data accuracy may not meet the user requirement in varying organization. This paper aims to develop a tool to assess the quality of GM data by comparing it with formal data such as spatial data from Mayoralty of Baghdad (MB). This tool developed by Visual Basic language, and validated on two different study areas in Baghdad / Iraq (Al-Karada and Al- Kadhumiyah). The positional accuracy was asses

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Publication Date
Mon May 01 2017
Journal Name
2017 Ieee International Conference On Electro Information Technology (eit)
A high-performance non-isolated DC-DC buck converter design based on wide bandgap power devices
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Publication Date
Mon Dec 31 2012
Journal Name
Al-khwarizmi Engineering Journal
Genetic Algorithm Based PID Controller Design for a Precise Tracking of Two-Axis Piezoelectric Micropositioning Stage
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 In this paper, an intelligent tracking control system of both single- and double-axis Piezoelectric Micropositioner stage is designed using Genetic Algorithms (GAs) method for the optimal Proportional-Integral-Derivative (PID) controller tuning parameters. The (GA)-based PID control design approach is a methodology to tune a (PID) controller in an optimal control sense with respect to specified objective function. By using the (GA)-based PID control approach, the high-performance trajectory tracking responses of the Piezoelectric Micropositioner stage can be obtained. The (GA) code was built and the simulation results were obtained using MATLAB environment. The Piezoelectric Micropositioner simulation model with th

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Publication Date
Fri Jan 01 2016
Journal Name
8th Conference On Power Electronics, Machines And Drives (pemd), Glasgow, Uk
Design of tubular moving magnet linear alternator for use with an external combustion - free piston engine
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Publication Date
Sun Aug 01 2021
Journal Name
Journal Of Engineering
The Intelligent Auto-Tuning Controller Design Based on Dolphin Echo Location for Blood Glucose Monitoring System
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This paper presents an enhancement technique for tracking and regulating the blood glucose level for diabetic patients using an intelligent auto-tuning Proportional-Integral-Derivative PID controller. The proposed controller aims to generate the best insulin control action responsible for regulating the blood glucose level precisely, accurately, and quickly. The tuning control algorithm used the Dolphin Echolocation Optimization (DEO) algorithm for obtaining the near-optimal PID controller parameters with a proposed time domain specification performance index. The MATLAB simulation results for three different patients showed that the effectiveness and the robustness of the proposed control algorithm in terms of fast gene

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Publication Date
Sat Sep 30 2017
Journal Name
Al-khwarizmi Engineering Journal
A Cognitive Hybrid Tuning Control Algorithm Design for Nonlinear Path-Tracking Controller for Wheeled Mobile Robot
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Abstract

This research presents a on-line cognitive tuning control algorithm for the nonlinear controller of path-tracking for dynamic wheeled mobile robot to stabilize and follow a continuous reference path with minimum tracking pose error. The goal of the proposed structure of a hybrid (Bees-PSO) algorithm is to find and tune the values of the control gains of the nonlinear (neural and back-stepping method) controllers as a simple on-line with fast tuning techniques in order to obtain the best torques actions of the wheels for the cart mobile robot from the proposed two controllers. Simulation results (Matlab Package 2012a) show that the nonlinear neural controller with hybrid Bees-PSO cognitive algorithm is m

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Publication Date
Thu Dec 26 2019
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
The design of a proposed model for the application of the insurance policy for medical errors
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The aim of this study is to design a proposed model for a document to insure the mistakes of the medical profession in estimating the compensation for medical errors. The medical profession is an honest profession aimed primarily at serving human and human beings. In this case, the doctor may be subject to error and error , And the research has adopted the descriptive approach and the research reached several conclusions, the most prominent of which is no one to bear the responsibility of medical error, although the responsibility shared and the doctor contributes to them, doctors do not deal with patients according to their educational level and cultural and there are some doctors do not inform patients The absence of a document to insu

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Publication Date
Thu Nov 21 2019
Journal Name
Journal Of Engineering
A Neural Networks based Predictive Voltage-Tracking Controller Design for Proton Exchange Membrane Fuel Cell Model
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In this work, a new development of predictive voltage-tracking control algorithm for Proton Exchange Membrane Fuel Cell (PEMFCs) model, using a neural network technique based on-line auto-tuning intelligent algorithm was proposed. The aim of proposed robust feedback nonlinear neural predictive voltage controller is to find precisely and quickly the optimal hydrogen partial pressure action to control the stack terminal voltage of the (PEMFC) model for N-step ahead prediction. The Chaotic Particle Swarm Optimization (CPSO) implemented as a stable and robust on-line auto-tune algorithm to find the optimal weights for the proposed predictive neural network controller to improve system performance in terms of fast-tracking de

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Publication Date
Thu Dec 01 2011
Journal Name
Journal Of Engineering
OPTIMAL DESIGN OF MODERATE THICK LAMINATED COMPOSITE PLATES UNDER STATIC CONSTRAINTS USING REAL CODING GENETIC ALGORITHM
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The objective of the current research is to find an optimum design of hybrid laminated moderate thick composite plates with static constraint. The stacking sequence and ply angle is required for optimization to achieve minimum deflection for hybrid laminated composite plates consist of glass and carbon long fibers reinforcements that impeded in epoxy matrix with known plates dimension and loading. The analysis of plate is by adopting the first-order shear deformation theory and using Navier's solution with Genetic Algorithm to approach the current objective. A program written with MATLAB to find best stacking sequence and ply angles that give minimum deflection, and the results comparing with ANSYS.

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