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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 Feb 20 2019
Journal Name
Political Sciences Journal
National security and human security concepts in the study
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Security reflects a permanent and complex movement that complies with international and societal needs and developments in all its dimensions, interactions and levels. To constitute a universal demand for all States, communities and individuals. The question of security is one of the most important motivations and motivations that govern the behavior, and even the objectives of those societies and States. These groups or individuals have always sought to avoid fear and harm, and to provide stability, safety and security. In the light of this, security studies have been among the important fields of study in the field of international and strategic relations. The field witnessed many theoretical efforts, from the traditional perspective,

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Publication Date
Tue Sep 03 2019
Journal Name
Biochem. Cell. Arch.
CHLAMYDIA PNEUMONIAE INFECTION AND ENDOTHELIAL DYSFUNCTION IN CARDIOVASCULAR DISEASES
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This study designed to evaluate the relationship between the Matrix metalloproteinase -9(MMP-9), soluble Vascular endothelial cadherin(VE-CAD)and Chlamydia pneumonia infection in cardiovascular diseases patients. All blood sample were subjected for molecular detection of C.pneumoniae by using conventional polymerase chain reaction (PCR) depending on 16S rRNA while the level of serum MMP-9, VE-CAD measured by enzyme linked immunosorbent assay (ELISA). Seventy patients who suffering from cardiovascular diseases (angina, myocardial infraction and atherosclerosis) aged between 33-86 years have been investigated and compared to twenty of apparently healthy individuals as control group. Twenty six samples (37.14%) revealed positive results for C.

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Publication Date
Tue Feb 10 2009
Journal Name
مجلة كلية اللغات
relative pronoun in Hebrew language between ancient and modern
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Abstract The relative pronoun in Hebrew language is an important pronoun use anciently and recently, it developed and it's usage and meanings differed so, it was not confined to the particle "אֲשֶׁר" as a relative pronoun, but beside it appeared other pronouns giving the relative meaning. Hence, the topic of this research was on this basis through studying the relative pronouns in old and modern Hebrew, the way of using them and their connection with preposition particles, as well as studying the relative clause.

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Publication Date
Wed Jan 01 2020
Journal Name
International Journal Of Pharmaceutical Research
Spectrophotometric Evaluation of Paracetamol in Bulk and Pharmaceutical Preparations
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Publication Date
Wed Sep 02 2020
Journal Name
European Journal Of Molecular & Clinical Medicine
Omeg3 discovery, types, preparation, and application in medicinal life
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Publication Date
Fri Feb 15 2013
Journal Name
American Journal Of Health-system Pharmacy
Pharmacy in Iraq: History, current status, and future directions
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Publication Date
Thu Jun 09 2022
Journal Name
مجلة كلية الاداب جامعة بغداد
Khadija Al-Hadith and her scientific role in Iraq
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Khadija Al-Hadithi was known for her love of the Arabic language. She was a distinguished and serious phenomenon in Arabic science and culture. She was born in Basra Governorate, one of the ancient and important cities in the history of Arabic grammar and one of the centers of the intellectual and scientific movement. The Basra Grammar School emerged there and made numerous achievements in the field of Arabic linguistics that remain an important source for students of the specialty.

Publication Date
Wed Mar 15 2023
Journal Name
Al-academy
Decorative aesthetic aspects and their use in Islamic architecture
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The architecture of the richly decorated mosques demonstrated that the Islamic culture is one of the most significant and greatest civilizations in the history of humanity. The plant decorative units are one of the key areas in which the Muslim artist excelled. As a result, he created various plant forms that he took from nature, which led him to invent the arabesque art consisting of plant motifs with curved and rounded lines or wrapped between them. These shapes with curved borders include leaves, twigs, and flowers. Buildings and artefacts from the nineteenth century AD have this shape. they achieved their objectives during the twelfth and thirteenth centuries. There was another kind of vegetable decorative unit, made up of stems and

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Publication Date
Sun Dec 16 2018
Journal Name
Al-academy
Sculptural Formation in the Third Millennium: Styles and Trends
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The research studies the sculptural formation in the third millennium: styles and trends, by taking the most important results of sculpture in the third millennium. The problem of the research is to search for the new sculptural formation in what it constitutes of social and human importance, and what are the important factors in forming the   contemporary sculptural structure, and what is the mechanism of showing and producing the new formation. The research requires the study of the most important thing that the (sculptural formation in the third millennium styles and trends) represents. The importance of research depends on the importance of the sculptural formation after the twentieth century and the importance that the for

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Publication Date
Wed Feb 20 2019
Journal Name
Political Sciences Journal
Political Culture and Civil Society in Algeria: Problematic relationship
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In light of what constitutes the cultural factor from a great importance in the context of the incorporation of an active and participant civil society in the process of democracy- building and the achievement of political development, this article tries to look at the concept of the political culture and the civil society with the stand on the nature of existing relationship between them in its theoretical part, then the move to dissection of the civil society crisis in Algeria under the prevalent cultural values for understanding the relationship between the two variables in its empirical part, as a step towards the detection on the pivoting of democratic values in activating the political participation and attainment the democratic co

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