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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 01 2024
Journal Name
Iraqi Journal Of Hematology
Provisional diagnosis of clinically significant hemoglobinopathies and decision on suitability for marriage as part of the premarital screening program in Iraq: Iraqi Society of Hematology Guidelines
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Publication Date
Thu Nov 01 2018
Journal Name
Journal Of Economics And Administrative Sciences
Marketing decisions as an intermediary variable of the nature of the relationship between Environmental Turbulence and marketing effectiveness exploratory study of Carrefour branches in Erbil Governorate
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The organizations, represented by its Management, are working hard in various ways to identify the environmental disturbances that occur in their environment and to investigate and follow up the movement of these disturbances and to respond to them through the decisions they make in an attempt to keep pace with the work and sustainability of their activities, including those decisions, marketing decisions taken by the environmental disturbulence in the market of the organization, the inability of these organizations to read the indicators of these disturbulence correctly displays their marketing effectiveness to vibration and decline in the negative.The current research is based on a fundamental problem that envi

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Publication Date
Tue Mar 28 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Evaluation of Rosuvastatin Effect as Adjuvant Therapy to Methotrexate on Lipid Profile and the Possibility of its Cardioprotective Effect in Iraqi Patients with Active Rheumatoid Arthritis
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Rheumatoid arthritis (RA) is a common inflammatory disease that associated with increased morbidity and mortality due to accelerated atherosclerosis. Rosuvastatin is a unique hydroxy methyl glutaryl Co A (HMGCoA) reductase inhibitor that has anti inflammatory effects.

The aim of this study was to evaluate the effect of rosuvastatin as adjuvant therapy to methotrexate (MTX) on lipid profile and its possible cardioprotective effect in RA patients. A double blinded placebo controlled clinical trial with 8 weeks follow up periods at which 40 patients with active RA using MTX were randomized into 2 groups to receive either rosuvastatin 10mg or placebo as adjuvant therapy to MTX. In addition to twenty healthy subjects as control group.

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Publication Date
Wed Mar 31 2021
Journal Name
Indones. J. Chem.,
Synthesis and DFT Study of the Complexation of Schiff Base Derived Curcumin and L-Tyrosine with Al(III), Ag(I), and Pb(II) Metal Ions
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The multi-dentate Schiff base ligand (H2L), where H2L=2,2'-(((1,3,5,6)-1-(3-((l1-oxidaneyl)-l5-methyl)-4-hydroxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)hepta-1,6-di ene-3,5-diylidene)bis(azaneylylidene))bis(3-(4-hydroxyphenyl)propanoic acid), has been prepared from curcumin and L- Tyrosine amino acid. The synthesized Schiff base ligand (H2L) and the second ligand 1,10-phenanthroline (phen) are used to prepare the new complexes [Al(L)(phen)]Cl, K[Ag(L)(phen)] and [Pb(L)(phen)]. The synthesized compounds are characterized by magnetic susceptibility measurements, micro elemental analysis (C.H.N), mass spectrometry, molar conductance, FT-infrared, UV-visible, atomic absorption (AA), 13C-NMR, and 1H-NMR spectral studies. The characterization of the

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Publication Date
Tue Mar 25 2025
Journal Name
Indonesian Journal Of Chemistry
Synthesis, Characterization, and Antioxidant Activity of Cr(III), Mn(II), Fe(III), Co(II) and Ni(II) Complexes with Mixed Azo Dye and Bipyridyl Ligands
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Mixed ligands reaction of [2-[(3-hydroxyphenyl)diazinyl]-1,2-benzothiazol-3(2H)-one-1,1-dioxide] (H2L, primary ligand) and bipyridyl (secondary ligand) with salts of Cr(III), Mn(II), Fe(III), Co(II) and Ni(II) was performed. A series of air-stable complexes with distinctive octahedral moieties was created by equal molar ratio (1:1:1). The formation of these compounds was verified using detecting analysis techniques incorporating mass spectra, which validated the achieved geometries. Fourier transform infrared (FTIR) analysis demonstrated how the ligands (H2L and bipyridyl) are chelated as tridentate (ONO) and bidentate (NN) groups, respectively and the coordination with the metal ions. Thermal decomposition studies using pyrolysis (

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Publication Date
Sat Jun 25 2022
Journal Name
International Journal Of Drug Delivery Technology
Assessment of Serum Levels of the WNT Pathway Antagonist (Dickkopf-1) in a Sample of Type 2 Diabetic Patients with Retinopathy using Two Groups of Antidiabetics
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Objectives: Dickkopf-1 (DKK-1) is WNT/b-catenin pathway antagonist which plays a detrimental role in the development of diabetic retinopathy (DR). This research aimed to assess serum DKK-1 levels in diabetic patients who have and have not developed DR and, compare them with the control subjects finding out whether we can use it as an indicator for DR early diagnosis and to find out which one of the widely used two groups of antidiabetic treatments had the greater effect on this biomarker and hence on the progression of DR. Methods: The study participants were divided into two subgroups: First, 70 patients (36 male, 34 female) with type 2 diabetes mellitus, among them 35 patients diagnosed with DR and 35 with no evidence of DR, and s

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Publication Date
Sat Dec 20 2025
Journal Name
Bulletin Of The Iraq Natural History Museum
MORPHOLOGICAL AND MOLECULAR DESCRIPTION FOR A NEW RECORD OF NEMATODE ACROBELOIDES VARIUS KIM, KIM & PARK, 2017 (RHABDITIDA, CEPHALOBIDAE) FROM IRAQ
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This study aimed to identify and describe one of the bacterial feeder nematode Acrobeloides varius Kim, Kim and Park, 2017 (Rhabditida, Cephalobidae), which was isolated from soil samples that were collected from Baghdad, central of Iraq, and was classified using both morphological and molecular criteria. All specimens of A. varius were cultured, identified and described using morphometric criteria. Selected specimens (Zah. IRQ3 OR994579.1 isolate) of this species were characterized by having the body length of the male ranging from (184.94 – 221.72 μm), the body length of the female ranging (507.38 – 521.92 μm) and the body length of the juvenile ranging from (355.53 – 490.35 μm). Selected specimens of this species were m

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Publication Date
Wed Apr 01 2020
Journal Name
Iop Conference Series: Earth And Environmental Science
Strategic Analysis of New Cities (Case Study Basmaya City - Republic of Iraq) An Analytical Study of Strength, Weakness, Opportunity, and Threat
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The rapid growth of cities and their inflation is a big problem, especially in the last years. this growth is accompanied by such problems like population growth, housing need, low level of services, random expansion, traffic congestion as well as pollution of the environment, which leads to a decline in the quality of life in Baghdad, the population are concentration in Baghdad therefore that leads to imbalance of development among cities and productive concentration for service projects in a mega cities, causing migration from other provinces In search of a better life. The main objective of the new cities is to relieve pressure on major cities and guide the growth of cities. Basmaya city it’s a new city project adopted f

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Publication Date
Wed Aug 01 2018
Journal Name
International Journal Of Electrochemical Science
Utilization of Natural Dyes from Zingiber officinale Leaves and Clitoria ternatea Flowers to Prepare New Photosensitisers for Dye-Sensitised Solar Cells
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Publication Date
Wed Jan 01 2020
Journal Name
Indian Journal Of Forensic Medicine And Toxicology
Continuous Flow Injection Analysis,Turbidmetric and Photometric Determination of Methyldopa Using a New Long Distance Chasing Photometer (NAG-ADF-300-2)
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A specific, sensitive and new simple method was used for the determination of methyldopa in pure and pharmaceutical formulations by using continuous flow injection analysis. This method is based on formation of ion pair compound between methyldopa and potassium hexacyanoferrate in acidic medium to obtain a yellow precipitate complex using long distance chasing photometer (NAG-ADF-300-2). The linear range for calibration graph was 0.05-35 mmol/L for cell A and 0.05-25 mmol/L for cell B, and LOD 1.4292 µg /200 µL for both cells with correlation coefficient (r) 0.9981 for cell A and 0.9994 for cell B, RSD% was lower than 0.5 % for n=8 for. The results were compared with classical method UV-Spectrophotometric at λ max=280 nm and turbi

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