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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
Sun Mar 31 2024
Journal Name
Association Of Arab Universities Journal Of Engineering Sciences
Using Solid Waste as A Substitute for Raw Materials in Construction: A Review.
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The main challenge is to protect the environment from future deterioration due to pollution and the lack of natural resources. Therefore, one of the most important things to pay attention to and get rid of its negative impact is solid waste. Solid waste is a double-edged sword according to the way it is dealt with, as neglecting it causes a serious environmental risk from water, air and soil pollution, while dealing with it in the right way makes it an important resource in preserving the environment. Accordingly, the proper management of solid waste and its reuse or recycling is the most important factor. Therefore, attention has been drawn to the use of solid waste in different ways, and the most common way is to use it as an alternative

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Publication Date
Wed Jun 01 2022
Journal Name
Journal Of The College Of Languages (jcl)
The Existential Dilemma as a Philosophical Problem in The Beggar by Naguib Mahfouz
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     The Beggar (1965) is a story of isolation and depression which is written by the Egyptian novelist Naguib Mahfouz who is considered the father of Arabic Literature in the modern era. Specifically, he refers in his great novel called The Beggar that the man unable to achieve psychological revival after Nasser’s revolution, the man sacrificed his own job and his family for a desire that increases his feelings of alienation and depression which leads him to an emotional outcry against the indifferent. The main aim of the study highlights the concept of existential dilemma as a philosophical problem and personality crisis by the protagonist of The Beggar novel, Omer Al-Hamzawi who had acc

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Publication Date
Sat Jun 01 2013
Journal Name
Journal Of The College Of Languages (jcl)
HONOUR " IN SOMERSET MAUGHAM 'S A MAN OF HONOUR MAUGHAM AS A DRAMATIST
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Somerset Maugham is known mainly as a novelist . This paper presents Maugham the dramatist . Many critics have found him a promising dramatist . He has written 30 plays , then he turns his back upon the theater and writes his autobiographical and most successful novel Of Human Bondage ( 1915) .

        Maugham's writing is clear , precise , and simple . He is described as a realist who is keenly aware of human nature , its concentration and frustration . His only tragedy A Man of Honour is a play in 4 acts . This paper concentrates mainly on this play to show Maugham as a dramatist and to show his concept of " honour " .

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Publication Date
Wed Oct 30 2024
Journal Name
Iraqi Journal Of Science
Evaluation of the Activity of Olibanum Oil as an Immune Booster in Rats
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The applications of herbal medicine have recently acquired growing interest in range of the prophylaxis and treatment of diseases. Olibanum has been used since ancient eras and several reports studied the pharmacological characteristics of boswellic acid, particularly their effect on the inflammatory response, analgesic properties, and anti-arthritic activity mostly in cell lines, but new approaches include animal models to assess these natural derivatives effects taking into consideration of being safer than synthetic preparations.  The impact of olibanum oil on several parameters was studied in rats during this study. These included white blood cell (WBC) count, lactate dehydrogenase (LDH), and C reactive protein (CRP), as well a

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Publication Date
Mon Mar 15 2021
Journal Name
The Journal Of Legal And Social Sciences
The Limitations on the Judge’s Authority in Judicial Interpretation – France as a Model
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When exercising their authority in the jurisprudence, judges are subject to a set of restrictions that they must adhere to, as they do not want their jurisprudence to be accepted and welcomed by law practitioners in general, and legal scholars in particular, and in contrast to it, the arrows of criticism and defamation will extend to that jurisprudence, and then they will have to reverse them . Perhaps the most important of those restrictions imposed on judges is their observance of justice between the parties to the lawsuit through their lack of bias for one of the parties at the expense of the other, in addition to their observance of public order and public morals, as well as their observance of the legal texts that they work under its u

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Publication Date
Tue Aug 15 2023
Journal Name
Journal Of Economics And Administrative Sciences
Industries Based on the Petrochemical Industry in Iraq-Plastics Industry as a Model
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This study came to discuss the subject of industries dependent on petrochemical industries in Iraq (plastic as a model) during the period 2005–2020, and the study concluded that the plastic industries contribute to areas of advancement and progress and opportunities to deal efficiently with the challenges posed by the new variables, the most important of which is the information revolution. communications and trade liberalization, and this is what contributes to the competitiveness of these industries. And because the petrochemical industry in Iraq has an active role in establishing plastic industrial clusters and clusters of micro, small, and medium industries by providing the necessary feedstock for these industries in various fields

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Publication Date
Wed Feb 05 2014
Journal Name
Baghdad Science Journal
Study of Plasma Metanephrine Level As Biochemical Parameter in Pregnant Women with Preeclampsia
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Pregnancy- including hypertension(PIH), also known as preeclampsia, is one of the major causes of maternal and fetal death. This study was carried out on 30 pregnant women with preeclampsia and 30 healthy pregnant women as control ranging in age mean ±SD (28.84±3.55) years , BMI (76.80±9.78) Kg/m2 and gestation age(30.82±0.75)week. The aim of this research was studied the plasma Metanephrine level and other biochemical parameters such as Hemoglobin(Hb), serum Protein, S. Albumin, Globulin, Albumin/Globulin ratio (Alb/Glu. ratio), S.Glutamate Pyruvate aminotransferase (GPT), S.Glutamate Oxaloacetate aminotransferase(GOT). The obtained results have been compared with 30 healthy pregnant women as control group. The result showed that ther

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Publication Date
Fri Nov 09 2018
Journal Name
Iraqi National Journal Of Nursing Specialties
Promoting Clinical Breast Examination as A screening Tool for Breast Cancer in Iraq
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Breast cancer constitutes about one fourth of the registered cancer cases among the Iraqi population (1)
and it is the leading cause of death among Iraqi women (2)
. Each year more women are exposed to the vicious
ramifications of this disease which include death if left unmanaged or the negative sequels that they would
experience, cosmetically and psychologically, after exposure to radical mastectomy.
The World Health Organization (WHO) documented that early detection and screening, when coped
with adequate therapy, could offer a reduction in breast cancer mortality; displaying that the low survival rates
in less developed countries, including Iraq, is mainly attributed to the lack of early detection programs couple

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Publication Date
Sun Aug 01 2021
Journal Name
Journal Of Engineering
Reuse of Glass waste as a partial replacement to fine aggregates in concrete
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As human societies grow, the problem of waste management becomes one of the pressing issues that need to be addressed. Recycling and reuse of waste are effective waste management measures that prevent pollution and conserve natural resources. In this study, the possibility of using glass waste as an alternative was used as a partial weight substitute for fine aggregates with replacement ratios of 10, 20, 30, and 40% by the weight, and formed into test models (15 cm * 15 cm ) cube and (15 cm * 30 cm) cylinder, then matured and tested their strength compression and tensile strength at the age of 7 and 28 days and compared with a reference or conventional concrete with a mixing ratio (1: 1.5: 3) as well as testing its worka

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Publication Date
Mon May 28 2018
Journal Name
Iraqi Journal Of Science
Use Citrus aurantium plant as bio-indicator of air pollution in Baghdad city
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The current study was conducted to demonstrate the effects of air pollution on different biochemical parameters inCitrus aurantium plant and calculation the Air Pollution Tolerance Index (APTI). Five sites were selected tocollect plant leaves, four of them within the city of Baghdad, namely Al-Jadriya, Al-Andlous, Al-Doura and closeto the private generators to represent the urban areas and Abu Ghraib site to represent the rural area. Seasonalsamples were collected for the period from October 2016 to June 2017. Eleven biochemical parameters totalchlorophyll, ascorbic acid, leaf extract pH, relative water content, total nitrogen, total protein content, total sugarcontent, proline, electrical conductivity, cadmium and lead. The results of Citr

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