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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 Nov 01 2014
Journal Name
Journal Of Cosmetics, Dermatological Sciences And Applications
Genital Warts in Infants and Children—Re-Evaluation of Podophylline 15% as an Effective Topical Therapy
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KE Sharquie, AA Noaimi, MN Almallah, Journal of Cosmetics, Dermatological Sciences and Applications, 2014 - Cited by 2

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Publication Date
Thu Dec 15 2022
Journal Name
Al-academy
The dramatic act and its transformations in the Iraqi theatrical show "Black Astronomy play as a sample"
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The subject of the act and its transformations in the presentation is of great importance at the level of study, analysis and interpretation, and through that the researcher adopted the following title (The Dramatic Act and Its Transformations in the Iraqi Theatrical Show). The play of Black Astronomy was chosen as a sample for analysis, and the aim of the research came in order to achieve a special knowledge of the extent of the transformation that occurred between the dramatic structure of the act and theatrical embodiment and its multiple elements of operation in the Iraqi theatrical shows. It was limited to the show of the Iraqi theater in the year (2020) and included the theoretical framework that accommodated three sections. As for

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Publication Date
Mon Jan 02 2017
Journal Name
Al-academy
The semiology of culture and the sign variable in a theatre performance: Iraqi theatre as an example
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The culture of theatre performance has a vital role in the process of reading the linguistic and visual signs of the performance. And the process of transforming a theatre performance from its original context into a new hosting cultural context starts from the actual reading of the text. Directors derives their new signs out of his personal culture, depending on the society where they lives and the culture that forms the social conventions, traditions and beliefs. The text is usually written within its own historical and temporal culture. The process of its production usually takes it away from its original culture, when it interprets the codes of the original writer and their visual and linguistic signs and instils new alternative sign

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Publication Date
Sun Jan 01 2017
Journal Name
Medical Journal Of Babylon
His- Ventricle (HV) Interval And Syncope As Predictor For Pacemaker Implantation In Patients With Bifascicular Block (BFB)
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Transient drop in the heart beat or transient heart block (AVB) may be consider the main cause of syncope or presyncope inpatients with bifascicular block and syncope According to the Guidelines for cardiac pacing pacemaker consider part of treatment. Aims of our study were to evaluate whether there is role for EPS in patients BFB and to evaluate the symptoms after pacing. 42 patients were enrolled in this study, with mean age value (63.4± 12.2years), suffer from interventricular conductive defect and syncope; patients underwent EPS on admission time, and pacemaker implantation accordingly and programmed follow up for the device in the last four years. Our patients were 25 (59.5%) male and 17 (40.5%)female, all of them with syncope o

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Publication Date
Sun Jan 01 2023
Journal Name
International Journal Of Hydrogen Energy
Test of conductor and semiconductor electrocatalysts in high voltage alkaline electrolyzer as production media for green hydrogen
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Publication Date
Wed Aug 17 2022
Journal Name
Aip Conference Proceedings
The effect of using Gaussian, Kurtosis and LogCosh as kernels in ICA on the satellite classification accuracy
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This study focusses on the effect of using ICA transform on the classification accuracy of satellite images using the maximum likelihood classifier. The study area represents an agricultural area north of the capital Baghdad - Iraq, as it was captured by the Landsat 8 satellite on 12 January 2021, where the bands of the OLI sensor were used. A field visit was made to a variety of classes that represent the landcover of the study area and the geographical location of these classes was recorded. Gaussian, Kurtosis, and LogCosh kernels were used to perform the ICA transform of the OLI Landsat 8 image. Different training sets were made for each of the ICA and Landsat 8 images separately that used in the classification phase, and used to calcula

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Publication Date
Fri Apr 01 2022
Journal Name
Desalination And Water Treatment
MgCl2 and MgSO4 as draw agents in forward osmosis process for East Baghdad oilfield produced water treatment
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This study investigated a novel application of forward osmosis using different types of draw solutions for oilfield produced water treatment from the East Baghdad oilfield affiliated to the Midland Oil Company (Iraq). Magnesium chloride (MgCl2) and magnesium sulfate (MgSO4) were used as draw solutions in forward osmosis process to evaluate their effectiveness. Experiments were conducted in a laboratory scale forward osmosis system with cellulose triacetate hollow fiber membrane. In this work, sodium chloride solution was used as a feed solution with a concentration of 76 g/L (same concentration as the East Baghdad oilfield produced water) and the applied external pressure on the feed solution side was 2 bar. The impact of draw solution (DS)

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Publication Date
Fri Mar 01 2024
Journal Name
الذكوات البيض
The problem of employing political discourse and its role in promoting community peace: Iraq as a model
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After 2003, Iraq witnessed new challenges represented by the predominance of sectarian discourses, hatred and extremism at the expense of moderate political discourse and the predominance of sub-affiliations and external agendas at the expense of national affiliation, which led to the creation of an unsafe or stable environment dominated by the character of violence and terrorism. Moderate discourse would work to fuse sub-affiliations into one melting pot in which it would be the first loyalty to the homeland and not to the tribe, party or sect... Etc., and this in turn will contribute to promoting peaceful coexistence between the various other sub-affiliations within the framework of one community construction

Publication Date
Thu Jan 01 2026
Journal Name
Research On Crops
Effect of organic acid, amino acids and nano-fertilizer on growth, yield and nitrate concentration of lettuce plant under two farming systems
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Publication Date
Sat Jan 01 2022
Journal Name
Applied Ecology And Environmental Research
EFFECT OF SPRAYING WITH FOLIC ACID AND YEAST EXTRACT ON THE GROWTH, YIELD AND CALCIUM OXALATE CONCENTRATION OF SPINACH (SPINACIA OLERACEA L.)
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