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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 Dec 30 2024
Journal Name
Iraqi Journal Of Science
Synthesis, Characterization, Thermal Studies, and Antioxidant Activities of Azo Dye[2-[(3-Hydroxyphenyl)diazinyl]-1,2-Benzothiazol-3(2H)-one-1,1-Dioxide]and Metal Ion Complexes
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The new azo dye was synthesized via the reaction of the diazonium salt form of 3-aminophenol with 2-hydroxyquinoline. This dye was then used to access a series of complexes with the chlorides of manganese, iron, zinc, cadmium, and vanadium sulfate. The prepared ligand and its complexes were characterized by FT-IR spectroscopy, UV-visible spectroscopy, mass spectrometry, thermogravimetric analysis, differential scanning calorimeter, and microelemental analysis. Conductivity, magnetic susceptibility, metal content, and chlorine content of the complexes were also measured. The ligand and cadmium complex were identified using1H NMR and 13C NMR spectroscopy. The results showed that the shape of the ligand is a trigonal planner, and the c

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Publication Date
Sun Jul 01 2001
Journal Name
Bulletin Of The Iraq Natural History Museum (p-issn: 1017-8678 , E-issn: 2311-9799)
New record of ground pearls, Porphyrophora tritici (Bod.) (Homoptera, Margarodidae) as a pest of wheat in Iraq
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The ground pearls, Porphyrophora tritici (Bod.) is a new insect pest on wheat recorded for
the first time from Mousl Province, North of Iraq.

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Publication Date
Sun Mar 07 2010
Journal Name
Baghdad Science Journal
Synthesis, characterization and antimicrobial Studies of complexes of some metal ions with 5(2-hydroxy benzylidine) -2-thio ether -1, 3, 4-thiadiazole
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A new series of Fe (III) , Co (II) , Ni (II) and Cu (II) complexes of the Schiff base, 5 (2-hydroxy benzylidine) -2-thio ether -1, 3, 4-thiadiazole were prepared and characterized .The imine behaves as a bidentate. The nature of bonding and the stereochemistry of the complexes were deduced from metal analyses, infrared, electronic spectra,magnetic susceptibility and conductivity measurements, an octahedral geometry was suggested for all complexes except the copper complex has a square planar geometry .preliminary in vitro tests for antimicrobial activity show that all the prepared compounds except iron complex display good activity to gram positive Staphelococcus aures and gram negative Escherchia coli.

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Publication Date
Sun Mar 01 2015
Journal Name
Journal Of The Chilean Chemical Society
NEW AZO-SCHIFF BASE DERIVED WITH Ni(II), Co(II), Cu(II), Pd(II) AND Pt(II) COMPLEXES: PREPARATION, SPECTROSCOPIC INVESTIGATION, STRUCTURAL STUDIES AND BIOLOGICAL ACTIVITY
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The coordination ability of the azo-Schiff base 2-[1,5-Dimethyl-3-[2-(5-methyl-1H-indol-3-yl)-ethyl imino]-2-phenyl-2,3-dihydro-1H-pyrazol-4-ylazo]-5- hydroxy-benzoic acid has been proven in complexation reactions with Co(II), Ni(II), Cu(II), Pd(II) and Pt(II) ions. The free ligand (LH) and its complexes were characterized using elemental analysis, determination of metal concentration, magnetic susceptibility, molar conductivity, FTIR, Uv-Vis, (1H, 13C) NMR spectra, mass spectra and thermal analysis (TGA). The results confirmed the coordination of the ligand through the nitrogen of the azomethine, Azo group (Azo) and the carboxylate ion with the metal ions. The activation thermodynamic parameters, such as ΔE*, ΔH*, ΔS*, ΔG*and K are cal

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Publication Date
Sun Nov 01 2020
Journal Name
Iop Conference Series: Materials Science And Engineering
Assessment of some mechanical properties of PMMA/silica/zirconia nanocomposite as a denture base material
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Abstract<p>In this research, nanocomposites of poly(methyl methacrylate) (PMMA) and a mixture of nano silica (SiO<sub>2</sub>) and nano zirconia (ZrO<sub>2</sub>) were prepared in different weight percentages of the nano fillers to improve some of the properties of PMMA resin to be used as a denture base material. The nano filles were surface modified with a coupling agent and added to the PMMA in different amounts. Impact strength, transverse strength, hardness and roughness were tested for both control and experimental groups. The results indicate that PMMA/silica/zirconia nanocomposites, prepared with 5% by weight of both types of fillers, had a slight increase in impact s</p> ... Show More
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Publication Date
Mon Mar 27 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Synthesis of some Novel Nitrogenous Heterocyclic Compounds with Expected Biological Activity as Antimicrobial and Cytotoxic Agents
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This study includes synthesis of some nitrogenous heterocyclic compounds linked to amino acid esters or heterocyclic amines that may have a potential  activity as antimicrobial and/or cytotoxic.  Quinolines are an important group of organic compounds that possess useful biological activity as antibacterial, antifungal and antitumor .8-Hydroxyquinoline (8-HQ) and numerous of its derivatives exhibit potent activities against fungi and bacteria which make them good candidates for the treatment of many parasitic and microbial infection diseases.

These pharmacological properties of quinolones  aroused our  interest in synthesizing several new compounds featuring heterocyclic rings of the quinoline derivatives linke

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Publication Date
Sun Oct 01 2023
Journal Name
Baghdad Science Journal
Green synthesis of CdS:Sn NPs by Starch as a Covering Agent and Studying its Physical Properties
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The aim of this research is to employ starch as a stabilizing and reducing agent in the production of CdS nanoparticles with less environmental risk, easy scaling, stability, economical feasibility, and suitability for large-scale production. Nanoparticles of CdS have been successfully produced by employing starch as a reducing agent in a simple green synthesis technique and then doped with Sn in certain proportions (1%, 2%, 3%, 4%, and 5%).According to the XRD data, the samples were crystallized in a hexagonal pattern, because the average crystal size of pure CdS is 5.6nm and fluctuates in response to the changes in doping concentration 1, 2, 3, 4, 5 %wt Sn, to become   4.8, 3.9, 11.5, 13.1, 9.3 nm respectively. An increase in crystal

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Publication Date
Wed Mar 10 2021
Journal Name
Baghdad Science Journal
Synthesis of Novel N-Substituted Dimethylmaleimidyl Esters and Their Applications as Plasticizers for Poly(Vinyl Chloride)
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Three N-(hydroxylphenyl) dimethylmaleimides were directly prepared in good yields (81-86)% from the reaction of dimethylmaleic anhydride with amino phenols. The prepared imides were esterified to the corresponding benzoates, methacrylates and cinnamates via their reaction with different acid chlorides in the presence of triethylamine. The prepared esters were tested as plasticizers for PVC via preparing of thirty six samples of PVC with the prepared esters in certain weight ratio followed by recording their softening points. Comparison the results with the universal plasticizers for PVC (DOP) and (DBP) indicated that the prepared esters in general have high plasticizing efficiency.

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Publication Date
Sun Sep 01 2019
Journal Name
Baghdad Science Journal
A New Method for the Isolation and Purification of Trigonelline as Hydrochloride from Trigonella foenum-graecum L.
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Separation of Trigonelline, the major alkaloid in fenugreek seeds, is difficult because the extract of these seeds usually contains Trigonelline, choline, mucilage, and steroidal saponins, in addition to some other substances. This study amis to isolate the quaternary ammonium alkaloid (Trigonelline) and choline from fenugreek seeds (Trigonella-foenum graecum L.) which have similar physiochemical properties by modifying of the classical method. Seeds were defatted and then extracted with methanol. The presence of alkaloids was detected by using Mayer's and Dragendorff's reagents. In this work, trigonilline was isolated with traces of choline by subsequent processes of purification using analytical and preparative TLC techniques.

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Publication Date
Fri Dec 31 2021
Journal Name
Iraqi Journal Of Market Research And Consumer Protection
ULATRAVIOLET ABSORBANCE SEPECTRA FOR ANTIBIOTIC DERIVATIVES (AMINO GLYCOSIDES) USED IN MEDICAL AND PHARMACEUTICAL INDUSTRY: ULATRAVIOLET ABSORBANCE SEPECTRA FOR ANTIBIOTIC DERIVATIVES (AMINO GLYCOSIDES) USED IN MEDICAL AND PHARMACEUTICAL INDUSTRY
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Ultraviolet spectrophotometric studies for antibiotic (amino glycoside) derivatives including, Neomycin, Streptomycin, Gentamycin and Kanamycin with special reagents, which are benzoyl chloride; benzene sulfonyl chloride, toluenesulfonyl chloride and phthalic anhydride were made. Amino glycosides derivatives were followed through measurements of the ultraviolet absorbance (A) from which the absorptivity (ε) of the complexes was deduced and molar absorbances using Ultraviolet for products and calculate the number of reagents molecule that combine to amino glycosides.

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