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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 Jun 14 2023
Journal Name
Al-academy
fashion and Contrasting in the contemporary Iraqi theater show
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Since its inception, the theatrical performance has been based on the principle of permanence, continuity, renewal and innovation in the structure of its visual elements. These innovations and the effectiveness of continuity cannot be achieved without searching for everything that is new and different at the level (form and content) in order to create an image with innovative and effective features in the theatrical discourse, and from Among the elements of the theatrical performance (theatrical costumes) that have been subject to variation since the beginning of the theater until now, and for this purpose, the current research was conducted with the question of the research problem: What are the variations of costumes in the contemporar

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Publication Date
Thu Jun 15 2017
Journal Name
Journal Of Baghdad College Of Dentistry
CD34 and Wnt3 expression in potentially malignant oral disorders
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Background: Potentially malignant oral disorders (PMODs) are common precursors of oral squamous cell carcinoma (OSCC). Neoangiogenesis and signalling are important intermediate biomarkers that may govern the progression of dysplastic mucosa into carcinoma. Aims: Evaluate the importance of CD34 and Wnt3 expression in PMODs and OSCCs in relation to their clinicopathological parameters. Settings and Design: Prospective cross-sectional study. Materials and Methods: Immunohistochemical staining for CD34 and Wnt3 was performed for 41 samples. These included 27 PMODs, six OSCCs and eight normal gingival and alveolar mucosa. Analysis of variance (ANOVA) and post-hoc tests were applied. P<0.05 was considered statistically significant. Results: CD34

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Publication Date
Fri Jul 01 2016
Journal Name
Al–bahith Al–a'alami
The Color and its Semiotic Reflections in Iraqi Newspapers.
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The Colour is one of important aspect of human activity, especially in General arts and press, and also is one of the essential elements to achieve and build the idea of design technology in the appropriate places, according to the space of designs work.
In a view of the colour and its relationship with the Semiotics, we can find that the objectives goals at the point of visual formats that’s «oral or written”. In last years, the intellectual concerns of Semiotics through eye contact methods, that’s meaning contact methods for get messages of sense of sight.
The semiotics term Can be defined into: (the sequential feature or network system has relations according agreed language rules, in a particular environment, also is a g

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Publication Date
Tue Jun 20 2023
Journal Name
مجلة كلية التربية للبنات – الجامعة العراقية ،ت
Use of collocant food items in Arabic and English
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This paper investigates the collocational use of irreversible food binomials in the lexicons of English (UK) and Arabic (Iraq), their word-order motivations, cultural background, and how they compare. Data consisted in sixteen pairs in English, versus fifteen in Arabic. Data analysis has shown their word order is largely motivated by logical sequencing of precedence; the semantically bigger or better item comes first and the phonologically longer word goes last. These apply in a cline of decreasing functionality: logical form first, semantic importance second, phonological form last. In competition, the member higher in this cline wins first membership. While the entries in each list clearly reflect culturally preferred food meals in the UK

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Publication Date
Tue Jan 29 2019
Journal Name
Journal Of The College Of Education For Women
Suggestibility in Kindergarteners and its relation to some variables
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The childhood of the most important stages throughout the human and which have been more vulnerable to various factors surrounding it and with the scientific and cognitive development in all fields surfaced many psychological phenomena that play a large role in influencing children and their behavior trends is the susceptibility of the lure of psychological phenomena which plays a major role in the social attitudes of individuals it may not be predictable so that individuals vary in between them in terms of vulnerability Balasthoa You do this only _bl that the same individual at different influenced Balasthoa different depending on the positions and this was research to achieve its objectives and that are known:
_ alasthoa The childre

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Publication Date
Wed Nov 13 2024
Journal Name
Aip Conference Proceedings
On Sδ.derived and Sδ.isolated sets in supra topological spaces
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The topic of supra.topological.spaces considered one of the important topics because it is a generalization to topological.spaces. Many researchers have presented generalizations to supra open sets such as supra semi.open and supra pre.open sets and others. In this paper, the concept of δ∼open sets was employed and introduced in to the concept of supra topology and a new type of open set was extracted, which was named S∼δ∼open. Our research entails the utilization of this category of sets to form a new concepts in these spaces, namely S∼δ∼limit points and S∼δ∼derive points, and examining its relationship with S∼open and S∼reg∼open. Based on this class of sets, we have introduced other new concepts such as S∼isolate

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Publication Date
Tue Apr 22 2025
Journal Name
Passer Journal Of Basic And Applied Sciences
Searching Elastic and Inelastic Coulomb Transitions in Chromium-54
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Publication Date
Sun Mar 15 2020
Journal Name
Arab World English Journal
Pragmatics of Political Blame in British and Iraqi Parliaments
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This research is a pragmatic study of political blame in British and Iraqi Parliaments. It aims to unfold the similarities and/or differences in terms of the pragmatic and pragma-rhetorical strategies used by British and Iraqi politicians when they exchange blame in both offensive and defensive situations. A statistical analysis is conducted to quantitatively support the findings of the pragmatic analysis. The analyses conducted have yielded different results among blame is a process composed of two stages. Each stage is distinct for its pragmatic components and pragma-rhetorical strategies. British and Iraqi MPs at the blame stage tend to utilize impoliteness as their main strategy. However, British and Iraqi MPs perform differently at the

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Publication Date
Sun Mar 13 2011
Journal Name
Baghdad Science Journal
Studying some Immunological and Hormonal profiles in Infertile Male
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The present study was designed to evaluate the immunological status in a sample of Iraqi males with primary infertility and them age range18-55 years, who were attending the Centre of Infertility and in vitro Fertilization (Kamal Al-Samaraie Hospital, Baghdad) during the period December 2008 – April 2009. They were divided into three groups; 40 patients with anti-sperm antibodies (ASA), 20 patients with Asthenozoospermia (AST) and 20 patients with azoospermia (AZO). In adition to20 fertile males was as control group. The parameters of evaluations were standard seminal fluid analysis, anti-sperm antibodies and anti-mitochondrial antibodies in serum, Therefore, two types of samples were collected from each subject; seminal fluid and blood.

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Publication Date
Mon Nov 09 2020
Journal Name
Construction Research Congress 2020
How to Improve Workforce Development and Sustainability in Construction
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