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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
Sat Jun 25 2022
Journal Name
International Journal Of Drug Delivery Technology
Microneedles as A Magical Technology to facilitate Transdermal Drug Delivery: A Review Article
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Skin drug administration is the method used to provide drugs for local or systemic therapy, which is recognized for clinical usage. It is the third-largest method of medication delivery, after only intravenous administration and oral administration. Using a transdermal delivery method makes the administration easy, and blood concentration and adverse effects can be reduced. A microneedle is a micron-sized needle with a short height of no more than 500 micrometers and a width of no more than 50 micrometers. The needle comes into contact with the epidermal layer of the skin before it gets to the dermal layer, where there is no discomfort. Several materials, such as metals, inorganic, and polymer materials, are used to create microneed

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Publication Date
Sun Dec 01 2019
Journal Name
Al-ustath Journal For Human And Social Sciences
Landscape as History: A Postcolonial Ecopoetic Study of the Poetry of Derek Walcott
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Abstract: As human history is implicated in landscape or the natural history, it can be stated that the origins of the Caribbean writers' conflict, in general, are the colonial history of West India. That history which tells the story behind not only their fragmented identity, but also the problems connected to their language as well. Building on the arguments of the prominent Postcolonial ecoccritics such as Elizabeth DeLoughrey, George Handley, Helen Tiffin, and Graham Huggan, this research analyzes selected poems by Derek Walcott's which are bounded in his volume, Collected Poems. It shows how the Caribbean history has been erased due to the brutality of colonization offering landscape as a reliable source which has recorded that history

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Publication Date
Sat Jul 20 2024
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
Polyacrylonitrile Nanofiber Composites as Efficient Removal of Pollutants for Wastewater: A Review Article
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Polyacrylonitrile nanofiber (PANFS), a well-known polymers, has been extensively employed in the manufacturing of carbon nanofibers (CNFS), which have recently gained substantial attention due to their excellent features, such as spinnability, environmental friendliness, and commercial feasibility. Because of their high carbon yield and versatility in tailoring the final CNFS structure, In addition to the simple formation of ladder structures through nitrile polymerization to yield stable products, CNFS and PAN have been the focus of extensive research as potential production precursors. For instance, the development of biomedical and high-performance composites has now become achievable. PAN homopolymer or PAN-based precursor copolymer can

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Publication Date
Fri Jan 01 2016
Journal Name
Journal Of Cosmetics, Dermatological Sciences And Applications
Tuberculin as Intralesional Therapy for Viral Warts—Single-Blind, Split, Placebo, Controlled Study
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Publication Date
Fri Sep 30 2022
Journal Name
College Of Islamic Sciences
TYPES OF THINKING ACCORDING TO IBN AL-QAYYIM (Analytical Thinking as a Model)
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The human intellect and his ability to complex thinking is a characteristic that Allah has given him above all his creatures. Islam came to encourage the utilization of the mind by thought, contemplation and consideration of the kingdom of Allah, His signs and religion, and He gave us a set of legislation that preserves the mind and protects it from falling into error or deviation.

This research deals with one of the most important components of civilizations in general and Islamic civilization in particular, which is thinking and what is related to it. It is an essential and influential component in man's dealing with life around him and the for

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Publication Date
Wed Jul 01 2015
Journal Name
J Fac Med Baghdad
AH jump as predictor for successful Ablation of atrioventricular nodal reentrant tachycardia (AVNRT)
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Background: Atrioventricular nodal reentrant tachycardia (AVNRT) is the commonest regular supraventricular tachyarrhythmia. Ablation in the area of slow pathway (SP) has been successfully implemented in every day clinical electrophysiological practice for more than 20 years. Although the procedure is generally regarded as effective and safe, data on long-term effects and predictors of success or failure are incomplete.

Publication Date
Mon Feb 19 2018
Journal Name
Al-academy
Directing Techniques to Process the Radio Drama Script ( Khata'a Play as a Sample)
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     The radio drama is considered to be one of the arts that is discovered after a long period of theater's discovery. Initially , it was the broad framework of the theater's work when radio was broadcasting the shows on the huge theaters. This beginning encouraged many of the radio specialists to correlate plays with radio and make a novice and distinctive type of art. Thus, radio drama made its first step including the following   ( plays, short and long series drama as well as other types of radio arts). Because of the above mentioned , the researcher is stimulating  to study directing techniques to process the radio drama script ( Khata'a play as a sample).

The first chapter deals with the

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Publication Date
Sat Jan 05 2019
Journal Name
Iraqi Journal Of Physics
Characterization of (SnO2)1-x(TiO2:CuO)x films as NH3 gas sensor
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Tin dioxide (SnO2) were mixed with (TiO2 and CuO) with concentration ratio (50, 60, 70, 80 and 90) wt% films deposited on single crystal Si and glass substrates at (523 K) by spray pyrolysis technique from aqueous solutions containing tin (II) dichloride Dihydrate (SnCl2, 2H2O), dehydrate copper chloride (CuCl2.2H2O) and Titanium(III) chloride (TiCl3) with molarities (0.2 M). The results of electrical properties and analysis of gas sensing properties of films are presented in this report. Hall measurement showed that films were n-type converted to p- type as titanium and copper oxide added at (50) % ratio. The D.C conductivity measurements referred that there are two mechanisms responsible about the conductivity, hence it possess two act

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Publication Date
Mon Feb 01 2021
Journal Name
Journal Of Engineering
Decolorizing of Malachite Green Dye by Adsorption Using Corn Leaves as Adsorbent Material
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This paper presents the ability to use cheap adsorbent (corn leaf) for the removal of Malachite Green (MG) dye from its aqueous solution. A batch mode was used to study several factors, dye concentration (50-150) ppm, adsorbent dosage (0.5-2.5) g/L, contact time (1-4) day, pH (2-10), and temperature (30-60)   The results indicated that the removal efficiency increases with the increase of adsorbent dosage and contact time, while inversely proportional to the increase in pH and temperature. An SEM device characterized the adsorbent corn leaves. The adsorption's resulting data were in agreement with Freundlich isotherm according to the regression analysis, and the kinetics data followed pseudo-first-or

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Publication Date
Sun Dec 13 2020
Journal Name
Clinical And Experimental Dental Research
The efficacy of polyether‐ether‐ketone wire as a retainer following orthodontic treatment
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Abstract<sec><title>Objectives

To investigate the efficacy of polyether‐ether‐ketone (PEEK) wire as a fixed orthodontic retainer, by comparing its performance to other retainer wires and optimizing its adhesion to composite bonding materials.

Materials and methods

Retainer wires of 15 mm segments were used, PEEK wires were prepared in cylindrical form with 0.8 mm diameter, and had two surface treatments namely air‐abrasion and conditioning with adhesive system. Three different metallic retainer wires were used for comparison and three tests were performed; two tests measured debonding force and associated wire deflec

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