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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
Wed Dec 30 2009
Journal Name
Iraqi Journal Of Physics
Synthesis of Nanosilica Glass Activated by Erbium Ions, Spectroscopic studies
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Erbium, as optical probe, doped silicate sol-gel glass with
different Er concentrations was formed by wet chemical synthesis
method using ethanol, water and tetraethaylorthosilicate
[Si(OC2H5)4] precursor. Erbium ions were incorporated into silica
sol-gel matrix via dissolution of Erbium chloride solution into the
initial Si(OC2H5)4 precursor sol. Aluminum (Al) as a co-dopant was
added to the final precursor in the form of Aluminum chloride
(AlCl3) solution. The prepared samples were analyzed using atomic
absorption analysis, X-ray diffraction and spectroscopic tests. The
experimental results concerned with the transmission spectra suggest
that the final samples have a good transparency and homogeneity.
A

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Publication Date
Wed Nov 24 2021
Journal Name
International Journal Of Drug Delivery Technology
Comparison among the Synthesis of Some Azomethine Derivatives by Classical and Non-classical Methods
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الوصف In this time, most researchers toward about preparation of compounds according to green chemistry. This research describes the preparation of 2-fluoro-5-(substituted benzylideneamino) benzonitrile under reflux and microwave methods. Six azomethine compounds (B1-6) were synthesized by two methods under reflux and assisted microwave with the comparison between the two methods. Reflux method was prepared of azomethine (B1-6) by reaction of 5-amino-2-fluorobenzonitrile with some aldehyde derivatives with (50–100) mL of absolute ethanol and some quantity of GAA and time is limited between (2–5) hours with a yield between (60–70) percent with recrystallization for appropriate solvents. But the microwave-assisted method was synthe

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Publication Date
Fri Jun 25 2021
Journal Name
International Journal Of Drug Delivery Technology
Comparison among the Synthesis of Some Azomethine Derivatives by Classical and Non-classical Methods
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In this time, most researchers toward about preparation of compounds according to green chemistry. This research describes the preparation of 2-fluoro-5-(substituted benzylideneamino) benzonitrile under reflux and microwave methods. Six azomethine compounds (B1-6) were synthesized by two methods under reflux and assisted microwave with the comparison between the two methods. Reflux method was prepared of azomethine (B1-6) by reaction of 5-amino-2-fluorobenzonitrile with some aldehyde derivatives with (50–100) mL of absolute ethanol and some quantity of GAA and time is limited between (2–5) hours with a yield between (60–70) percent with recrystallization for appropriate solvents. But the microwave-assisted method was synthesized of co

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Publication Date
Sat Dec 10 2016
Journal Name
International Journal Of Current Microbiology And Applied Sciences
Synthesis, Characterization and Biological Evaluation of Penicillin Derivatives Complexes with Some Transition Metal Ions
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Publication Date
Thu Dec 09 2021
Journal Name
Revista Latinoamericana De Hipertension
Synthesis, chemical hydrolysis and biological evaluation of doxorubicin carbamate derivatives for targeting cancer cell
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Publication Date
Thu Jun 30 2022
Journal Name
International Journal Of Drug Delivery Technology
Comparison among the Synthesis of Some Azomethine Derivatives by Classical and Non-classical Methods
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Publication Date
Tue Oct 01 2024
Journal Name
Results In Chemistry
Microwave synthesis, density functional theory study and antiproliferative activity of the novel spiropyrazole derivatives
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Publication Date
Tue Jun 01 2021
Journal Name
Baghdad Science Journal
Experimental and Theoretical Study of Neomycin Sulfate as Corrosion Protection for Titanium in Acid Media
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        The experimental and theoretical methods were studied for inhibition of the corrosion titanium in HCl by using neomycin sulfate drug. The results of neomycin sulfate drug had good corrosion protection for titanium in hydrochloric acid and the inhibition efficiency (%IE) increasing with increasing concentration of drug because the neomycin sulfate drug had adsorption from acid solution on surface of titanium metal. The program of hyperchem-8.07 was used for theoretical study of the drug by molecular mechanics and semi-empirical calculations. Quantum chemical was studied drug absorption and electron transferred from the drug to the Titanium metal, also inhibition potentials of drug attachment with the (LUMO-HOMO) energy gap,

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Publication Date
Thu Jan 01 2015
Journal Name
International Journal Of Technical Research And Applications
SYNTHESIS OF DRUG CARRIER POLYACRYLIC ACID WITH SPACER GROUP
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Publication Date
Mon Jul 01 2013
Journal Name
Journal Of Saudi Chemical Society
Synthesis, characterization and in vitro antimicrobial activity of some novel 5-substituted Schiff and Mannich base of isatin derivatives
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With the aim of developing potential antimicrobials, a series of novel Ciprofloxacin methylene isatin derivatives incorporating different aromatic aldehydes were synthesized and characterized by FTIR, 1H NMR, Mass spectroscopy and bases of elemental analysis. In addition, the in vitro antibacterial and antifungal properties were tested against some human pathogenic microorganisms by employing the disc diffusion technique. A majority of compounds were showing activity against several of the microorganisms. The relationship between the functional group variation and the biological activity of the evaluated compounds is discussed. From comparisons of the compounds, 3c was determined to be the most active compound.

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