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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
Fri Jan 01 2010
Journal Name
International Journal Of Advanced Intelligence Paradigms
Assessing IRPS as an efficient pairwise test data generation strategy
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Publication Date
Sun Jun 01 2014
Journal Name
Baghdad Science Journal
Preparation of polymer thin film using as NH3 gas Sensor
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Polyaniline organic Semiconductor polymer thin films have been prepared by oxidative polymerization at room temperature, this polymer was deposited on glass substrate with thickness 900nm, FTIR spectra was tested , the structural,optical and electrical properties were studied through XRD ,UV-Vis ,IR measurements ,the results was appeared that polymer thin film sensing to NH3 gas.

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Publication Date
Sat Aug 01 2015
Journal Name
2015 37th Annual International Conference Of The Ieee Engineering In Medicine And Biology Society (embc)
Tsallis entropy as a biomarker for detection of Alzheimer's disease
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Publication Date
Wed Dec 30 2009
Journal Name
Iraqi Journal Of Physics
CuInS2 Ternary Compound as Absorption Layer for Solar Cell Fabrication
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Copper indium disulphide, CuInS2, is a promising absorber material for thin film photovoltaic which has recently attracted considerable attention due to its suitability to reach high efficiency solar cells by using low cost techniques. In this work CuInS2 thin films have been deposited by chemical spray pyrolysis onto glass substrates at ambient atmosphere, using different [Cu]/[In] ratio in the aqueous solutions at substrate temperature 3000C
and different annealing temperatures . Structural and optical properties of CIS films were analyzed by X-ray diffraction, and optical spectroscopy. Sprayed CIS films are polycrystalline with a chalcopyrite structure with a preferential orientation along the 112 direction and no remains of oxides

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Publication Date
Wed Jul 01 2015
Journal Name
Al–bahith Al–a'alami
Favorite TV Channels / as News Sources for Iraqi University Professors.
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The growing ability of Television to transfer and present events as they occur and sometimes transfer events alive makes it the most important sources to receive news and find out what is going on in the world. These channels form the importance of multiple sources and displayed content, especially news. What adds to the importance of the research is that the people under study are Iraqi professors
The problem of the study is represented by an essential inquiry about the favorite satellite channels to obtain news for Iraqi professors
The aims of the study are identified by finding out the most favorite satellite channels as a source of news for Iraqi professors and the habits of exposer to the news by them
The research is a des

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Publication Date
Sun Jul 01 2018
Journal Name
Journal Of Educational And Psychological Researches
Teaching difficulties of cities geography as perceived by female student
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The research aims to explore the difficulties that encounter teaching geography of cities as perceived by female students. A total of (113) third stage female students / Geography Dept / college of education for women were chosen as a sample for the study. To collect the required data, a questionnaire was used as an instrument; it consisted of six parts represent teaching difficulties. It was a three-point Likert scale instrument with 1 signifying ‘main difficulty, 2 ‘sub-difficulty, and 3 ‘no difficult'. The difficulties organized in descend order, to analyze data, SPSS tool was used. The results revealed that the difficulties of content ranged (2.15-1.18), difficulties of education techniques ranged (2.47-2.04), difficulties of t

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Publication Date
Mon Aug 01 2011
Journal Name
Journal Of Engineering
PROPERTIES OF HARDENED CONCRETE USING CRUSHED CLAY BRICK AS AGGREGATES
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This paper provides the result of an investigation to use of crushed clay brick as
aggregates in producing concrete. Eight different crushed clay brick aggregate concretes were
used in this investigation. Compressive strength, splitting tensile strength and pulse velocity of
crushed clay brick aggregates concrete were determined and compare to natural aggregate
concrete. The compressive strength of crushed clay brick aggregates concretes were always
lower than the compressive strength of natural aggregates concrete regardless the age of
concrete, but the crushed clay brick aggregates concrete showed better performance as the age of
concrete increases and average reduction in compressive strength were 33.5% at the age

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Publication Date
Sun Dec 06 2015
Journal Name
Baghdad Science Journal
Synthesis and Characterization of Some Metal Complexes with their Sulfamethoxazoleand 4,4'-dimethyl-2,2'-bipyridyl and study Cytotoxic Effect on Hep-2 Cell Line
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The ligand 4-amino-N-(5-methylisoxazole-3-yl)-benzene-sulfonamide(L1) (as a chelating ligand) was treated with Pd(II),Pt (IV) and Au(III) ions in alcoholic medium in order to prepare a series of new metal complexes. Mixed ligand complexes of this primary ligand were prepared in alcoholic medium in presence of the co-ligand 4,4'-dimethyl-2,2'-bipyridyl(L2) with Cu(II) ,Pd(II) and Au(III) ions. The complexes were characterized in solid state using flame atomic absorption, elemental analysis C.H.N.S, FT-IR, UV-Vis Spectroscopy, conductivity and magnetic susceptibility measurements. The nature of some complexes formed in ethanolic solution has been studied following the molar ratio method, also stability constant was studied and the complexes f

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Publication Date
Tue Sep 11 2018
Journal Name
Iraqi Journal Of Physics
Synthesis and characterization of ligands derived 2-hydroxy-1- naphthaldehyde and their complexes with divalent metal ions (Mn+2, Fe+2, Ni +2)
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In this work, Schiff base ligands L1: N, N-bis (2-hydroxy-1-naphthaldehyde) hydrazine, L2: N, N-bis (salicylidene) hydrazine, and L3:N –salicylidene- hydrazine were synthesized by condensation reaction. The prepared ligands were reacted with specific divalent metal ions such as (Mn2+, Fe2+, Ni2+) to prepare their complexes. The ligands and complexes were characterized by C.H.N, FT-IR, UV-Vis, solubility, melting point and magnetic susceptibility measurements. The results show that the ligands of complexes (Mn2+, Fe2+) have octahedral geometry while the ligands of complexes (Ni2+) have tetrahedral geometry.

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Publication Date
Thu Mar 08 2018
Journal Name
Iosr Journal Of Applied Chemistry
synthesis, Composition, Spectral, Geometry and Antibacterial Applications ofMn(||),Ni(||),Co(||),Cu(||) and Hg(||) schiff Base complexes of N2O2 mixed donor with 1,10-phenanthroline
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synthesis, Composition, Spectral, Geometry and Antibacterial Applications ofMn(||),Ni(||),Co(||),Cu(||) and Hg(||) schiff Base complexes of N2O2 mixed donor with 1,10-phenanthroline