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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 Dec 29 2021
Journal Name
Journal Of The College Of Education For Women
Professional Development and its Relationship with some Variables in the Light of Sullivan Theory among Male and Female Teachers in the Basic Education Schools in Sultanate of Oman: سالم بن ناصر بن سعيد الكحالي
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The study aims to reveal the level of professional development in basic education schools from the male and female teachers’ viewpoint in the Sultanate of Oman. It further aims to examine its relationship with some variables in light of Sullivan theory, and the differences in the level of professional development (teachers’ skills, professional participation, professional development problems) according to the gender variable, and the educational stage (first cycle/ second cycle). The study sample consisted of (93) teachers distributed as such: (46) male teachers, and (47) female teachers. A questionnaire was prepared and applied to measure the level of the professional development of the male and female teachers. The questionnaire c

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Publication Date
Wed Jan 01 2025
Journal Name
Modern Sport
Vertical Resistance and Its Relationship with Speed-Strength and Biomechanical Variables During the Takeoff Phase and the Performance of Selected Activities in Individual and Team Sports
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Jumping ability is a fundamental variable in many sports, as its execution requires an integration of muscular strength Q1 and certain biomechanical variables. This is particularly evident in gymnastics jumping events and jump shots in ball games, both of which rely on a high level of vertical resistance. Vertical resistance serves as an indicator of an athlete’s ability to overcome their body weight while counteracting gravitational force to achieve optimal performance. As such, it is considered one of the key factors in movements that demand explosive power and speed. The researchers believe that despite the significant relationship between vertical resistance, speed-strength of the arms and legs, and certain biomechanical varia

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Crossref
Publication Date
Tue Jan 01 2019
Journal Name
Aip Conference Proceedings
Common fixed points and S-best coapproximation in 2-Banach spaces
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Publication Date
Thu Sep 15 2022
Journal Name
Al-academy
The philosophy of physical and sensory communication in the dramatic show
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Modern critical theories revealed polemical views about the reality of the existence of communication - as a necessity for building a deliberative discourse - in the theater or not. To the theory of communication with all the conditions it imposes on thinking, interaction, and emancipation of selves in different contexts.
Therefore, the current research included four chapters, the first chapter dealt with the research problem, which was represented in (the philosophy of sensory and physical communication in theatrical performance), and the first chapter included the importance of the research, its goal and its limits, and ended with defining the terminology, and the second chapter included (theoretical framework) the first topic (ph

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Publication Date
Thu Jun 30 2022
Journal Name
Gsc Biological And Pharmaceutical Sciences
Revision of public health and clinical importance of amoebiasis in Iraq
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Amebiasis, related to the pathogenic parasite Entamoeba histolytica, is a prominent cause of diarrhea globally. Amebiasis is primarily a disease of impoverished communities in developing nations, although it has recently arisen as a significant infection among returning tourists and immigrants. Severe cases are linked to a high case fatality rate. Although polymerase chain reaction (PCR)-based diagnosis is becoming more widely available, it is still underutilized. Treatment with nitroimidazoles is now suggested, however novel parasite medication research is a top priority. To avoid problems, amebiasis should be considered before corticosteroid therapy. Because there is no effective vaccination, sanitation and availability to clean w

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Publication Date
Mon Feb 01 2021
Journal Name
Neuroquantology
Study and Investigation of Hard Photons Emission in Heavy Ion Collisions
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This work involves hard photon rate production from quark -gluon plasma QGP interaction in heavy ion collision. Using a quantum chromodynamic model to investigate and calculation of photons rate in 𝑐𝑔 → 𝑠𝑔𝛾 system due to strength coupling, photons rate, temperature of system, flavor number and critical. The photons rate production computed using the perturbative strength models for QGP interactions. The strength coupling was function of temperature of system, flavor number and critical temperature. Its influenced by force with temperature of system, its increased with decreased the temperature and vice versa. The strength coupling has used to examine the confinement and deconfinement of quarks in QGP properties and inf

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Scopus (2)
Scopus
Publication Date
Tue Mar 28 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Prescribing Pattern and Rational use of Drugs in Maysan Governorate, Iraq
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This study was designed to investing the drug prescribing pattern which is the important point in the rational or irrational use of drugs among patients dispensing their prescriptions from the private pharmacies in Maysan governorate, Iraq for a period of 1 month. The data collected from prescriptions were calculated and analyzed according to the WHO prescribing guidelines. The data showed that the mean of drugs included in single prescription was 3.4, and 12% of prescribed drugs were written as generic names; moreover, the percentage of antibiotics, corticosteroids and anxiolytics were 33.3%, 11.4% and 23.8% respectively. Those results indicate the irrational use of drugs when compared with the world health organization standard values

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Publication Date
Sun Dec 02 2018
Journal Name
Journal Of The College Of Education For Women
Political Thought in Russia During the 21st Century, Targets and Features
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The features of strategic thought transformation in Russia based on attempt confirm the Russian influenced on Region of Eastern Europe through series of common defense treaties and mutual security between USSR and another states this treaties emphasis size on direct Russian supervision on these states in addition, Russia in trusted to formation communism regimes in its vital space, Russia inherited the status of former USSR in political and economic levels.

           Shortly we can see that Russia witnessed large Transformation in political strategic thought as a result of change in internal strategic environment and change of nature understanding which influenced on Russia. This

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Publication Date
Wed Jun 01 2022
Journal Name
Annals Of The Faculty Of Arts
Motivation and Second Language Acquisition: Motivational Orientations in Foreign Language Learning
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Numerous research studies have been conducted on why some learners acquire a second language more easily and quickly than others. Most of these studies have demonstrated that acquiring a second language does not depend only on learners’ cognitive ability or professional teaching strategies. The learning language process is more complicated than that. It is affected by crucial factors that are beyond the control of learners and teachers. These factors are known as sociolinguistic factors. These factors include culture, age, motivation, socio-economic status, and gender. This research paper mainly concentrates on the role of motivation in second language acquisition.

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Publication Date
Sun Nov 01 2015
Journal Name
Journal Of Cosmetics, Dermatological Sciences And Applications
Mycosis fungoides in iraqi patients—clinical, histopathological and immunohistochemical study
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HR Al-Hamamy, KE Sharquie, AA Noaimi, WS Abdulwahhab, Journal of Cosmetics, Dermatological Sciences and Applications, 2015 - Cited by 9

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