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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
Fri May 31 2019
Journal Name
Journal Of Engineering
Ornamentation and Modern Architecture in Iraq
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Despite the history of Baghdad city extends into a long history, most of the contemporary buildings of Baghdad have been shaped in the era of modernity. Furthermore, most of the buildings of modernity in Baghdad are types of modernity buildings in Iraq as a whole, and due to all the joints of change and development are taking place in Iraq starts from Baghdad. Accordingly, all selected buildings, which would be presented as case studies of modernity will be exclusively in Baghdad. Although the importance of this significant modernist product, which represents the identity of Baghdad, which should be preserved by the renewal and preservation policies, the problem of research was emerged as follow: new fin

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Publication Date
Thu Jun 03 2004
Journal Name
Journal Of Engineering
Heritage and Art Creativity in architecture
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Publication Date
Thu Dec 30 2021
Journal Name
Al-kindy College Medical Journal
Melatonin in male and female fertility
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Melatonin, a hormone synthesized mainly by the pineal gland, has been found in extra-pineal organs as well. It’s known as an organizer of circadian rhythms and more recently as an anti-oxidant. In addition to its role in maintaining immunity, pathophysiology of cardiovascular and neurological diseases, and as an anti-cancer agent, evidence has demonstrated that melatonin exerts a positive impact on male and female fertility primarily through oxygen scavenging effects. In In Vitro Fertilization (IVF) programs, supplementation of melatonin may be associated with better outcomes in terms of sperm quality, oocyte quality, embryo quality and pregnancy rates. This review summarizes various actions of melatonin on the body focusing on ma

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Publication Date
Thu Dec 30 2021
Journal Name
Al-kindy College Medical Journal
Melatonin in male and female fertility
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Melatonin, a hormone synthesized mainly by the pineal gland, has been found in extra-pineal organs as well. It’s known as an organizer of circadian rhythms and more recently as an anti-oxidant. In addition to its role in maintaining immunity, pathophysiology of cardiovascular and neurological diseases, and as an anti-cancer agent, evidence has demonstrated that melatonin exerts a positive impact on male and female fertility primarily through oxygen scavenging effects. In In Vitro Fertilization (IVF) programs, supplementation of melatonin may be associated with better outcomes in terms of sperm quality, oocyte quality, embryo quality and pregnancy rates. This review summarizes various actions of melatonin on the body focusing on male an

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Publication Date
Thu Jan 31 2019
Journal Name
Journal Of The College Of Education For Women
Urbanization and urban growth in Iraq
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The development issue is considered as one of the most important matters of concern to governments, intellectuals and specialists in the contemporary world, especially in developing countries that are trying hard to move out of the afflicting underdevelopment domain to a brighter future and achieve the aspirations of those countries through organized planning which take advantage of available resources, whether material or humanitarian, in the best way possible.
The development process are taking place at multiple levels ranging from national to regional to local where the community is stimulated and excited for the cooperation, participation and preparation to perform planned change in the methods of thinking, acting and production.<

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Publication Date
Wed May 17 2023
Journal Name
College Of Islamic Sciences
Time in (what and whatever) conditionals
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This is a research in which I studied the opinions of Arab scholars, in their studies
For (what) and (whatever) the two conditionals and their indication of time, and its name
B (time in (what) and (whatever) the two conditions), and I mentioned their opinions in it
This issue was discussed and discussed, and in this study it relied on the sources of the Arabic language.
Especially the books of grammar, interpretation, and the opinions of the scholars of the principles of jurisprudence are mentioned,
I also mentioned the opinion of the scholars of jurisprudence, and how they likened (whatever) to (everything).
In its indication of repetition, and as long as it indicates repetition, it indicates
time Because repetitio

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Publication Date
Sun Feb 03 2019
Journal Name
Journal Of The College Of Education For Women
The Babis and Baha’is in Iran
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The person who wants to learn. The history of Bab’is will notice a very
starnge phenomenon that they (Babis and Baha’is) resort to visions to prove their
delusion.
The believers usually reach to each other by their visions. This phenomenon
are shared among them from Al- Ahsa’ai time till the last phase of their propaganda
which is the Baha’is propaganda, and this is due to their ignorance and under
development in doctrine of islam which was widespread in Iran and the Islamic world.
The whole secrets of Babis and Baha’is movement were restricted among
particular group, most of them were Al- Rashti’s students and knew the basic
principles of their movement which deperding or (the principles) declarati

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Publication Date
Sat Oct 01 2022
Journal Name
Al–bahith Al–a'alami
Approaches in media, role and mobilization
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There is a natural problem raised by the issue of media performance. As a separate activity and express its own capabilities. This problem can be framed in the form of a question: Is media performance merely a reflection of the activity of other sectors of society, especially political and economic, and what links them to other societal sectors of interrelated relations? Is the media limited to mere transfer, or is it an industry with its own mechanisms and rules? The answer may seem somewhat complicated if we handle media with research and study in general, but the issue may be less complicated when it comes to Arab media, because its data may add another setback to the overall Arab setbacks.

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Publication Date
Wed Jan 01 2014
Journal Name
Journal Of The College Of Languages (jcl)
Hedges in Male and Female Language
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Hedging is a linguistic phenomenon used to convey interpersonal messages in spoken interaction. It is a communicative strategy which enables speakers to soften the force of utterances or moderate the assertive force of  utterances. It is resulted from different features such as uncertainty, doubt, tentativeness, ambiguity, neutrality, mitigation, and subjectivity. Hedging is used widely in  TV debates to make utterances more acceptable to the interlocutors. Hedges are expressions used to communicate the speaker's  weak commitment to information conveyed. The utterances in debates are often hedged because in an unhedged form  might sound threatening to the addressees, and, therefore, be likely to be rejected.

&

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Publication Date
Wed Feb 20 2019
Journal Name
Political Sciences Journal
Rationality and Freedom in Islamic Thought
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Abstract Rationality and freedom are fundamental elements of Western modernity. Although modern and contemporary Islamic thought has established its intellectual foundations on the fundamentals of intellectual thought that are at the core of its Islamic intellectual system, at the same time many of its intellectual products have been a response In spite of the fact that this Islamic intellectual response stands out from Western modernity as a negation or a positive attitude. The Islamic intellectual response differed in determining its position on Western modernity, depending on the nature of the historical stage that was The Islamic nation, as well as the nature of the challenge posed by Western civilization to other nations and other c

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