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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 Sep 01 2013
Journal Name
Baghdad Science Journal
Synthesis of Some Heterocyclic Compounds Derived from 2-Mercapto Benzoxazole
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New series of 2-mecapto benzoxazole derivatives (1-20) incorporated into fused to different nitrogen and suphur containing heterocyclic were prepared from 2-meracpto benzoxazole, when treated with hydrazine hydrate to afford 2-hydrazino benzoxazol (1). Compound (1) converted to a variety of pyridazinone andphthalazinone derivatives (2-4) by reaction with different carboxylic anhydride. Also, reaction of (1) with phenyl isothiocyanate and ethyl chloro acetate afforded 3-phenyl-1,3-thiazolidin-2,4-dione-2-(benzoxazole-2-yl-hydrazone) (6). Azomethines (7-10) were prepared through reaction of (1) with aromatic aldehyde, then (7, 8) converted to thaizolidinone derivatives (11, 12). Treatment of (1) with active methylene compounds afforded deriva

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Publication Date
Mon Feb 28 2022
Journal Name
Sains Malaysiana
Green Synthesis of Nickle Oxide Nanoparticles for Adsorption of Dyes
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The green synthesis of nickel oxide nanoparticles (NiO-NP) was investigated using Ni(NO3)2 as a precursor, olive tree leaves as a reducing agent, and D-sorbitol as a capping agent. The structural, optical, and morphology of the synthesized NiO-NP have been characterized using ultraviolet–visible spectroscopy (UV-Vis), X-ray crystallography (XRD) pattern, Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscope (SEM) analysis. The SEM analysis showed that the nanoparticles have a spherical shape and highly crystalline as well as highly agglomerated and appear as cluster of nanoparticles with a size range of (30 to 65 nm). The Scherrer relation has been used to estimate the crystallite size of NiO-NP which ha

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Publication Date
Sun Mar 01 2020
Journal Name
Fisheries & Aquatic Life
Directional fluctuating asymmetry in certain morphological characters as a pollution indicator: Tigris catfish (<i>Silurus triostegus</i>) collected from the Euphrates, Tigris, and Shatt al-Arab Rivers in Iraq
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Abstract<p>The relationship between pollution levels in river sediment and fluctuating asymmetry of resident silurid fish species, <italic>Silurus triostegus</italic> Heckel, was assessed. Eight bilateral body proportions were analyzed in 1,500 fish from eight river locations. Sediment pollution was measured based on the analysis of heavy metals (Cd, Cr, Cu, Ni, Pb and Zn) and organochlorine pesticides (DDT, DDD, DDE, chlordane, dieldrin, and lindane). The mean quotient approach (mERMq) was used to characterize sediment toxicity, which ranged from low to moderate levels for heavy metals and from low to severe for organochlorides. Variation was noted in the measurements of fish body mor</p> ... Show More
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Publication Date
Wed Dec 15 2021
Journal Name
Al-academy
The communicative education of fine arts in the COVID-19 crisis and its manifestations in the modernization of the works of the Iraqi painter "Nabil Ali as a model"
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 This study attempts to address the importance of communicative digitization in the field of various arts for the sake of continuity of shopping and aesthetic, artistic and intellectual appreciation of artistic achievements by the recipient on various places of their residence in light of the COVID 19 crisis, and to highlight the importance of the plastic arts of the Iraqi painter exclusively and how it expresses in a contemporary way the environment or life reality in Iraq in light of this crisis. With all its implications affecting the life reality from various aspects and methods of its negative and positive employment. As for the research procedures, the researcher reviewed the research methodology represented by the descriptive ana

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Publication Date
Tue Sep 17 2019
Journal Name
Journal Of The College Of Education For Women
A New Logic of Victory in Suzanne Collins’ The Hunger Games With Reference to Elements of Intertextuality in William Golding’s Lord of the Flies
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Suzanne Collins’ novel  The Hunger Games suggests a new logic of victory and set a distinguished focus on the unique personality of her heroin which brings to the mind the permanent correlation between all moral values. The Hunger Games World seems to be much more like one big bowl as it links the past, present, and the future. An Intertextual reference is interwoven in the present research as it brings Golding’s Lord of the Flies to the surface, and it highlights certain similarities between the two texts. In which Ralph, Piggy and Simon in Golding’s Lord of the Flies are the incarnations of stable moral values and hope of surviving ethics and rules in a chaotic and turmoil world. The event

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Publication Date
Mon Jul 01 2019
Journal Name
International Journal Of Swarm Intelligence Research
A New Strategy Based on GSABAT to Solve Single Objective Optimization Problem
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This article proposes a new strategy based on a hybrid method that combines the gravitational search algorithm (GSA) with the bat algorithm (BAT) to solve a single-objective optimization problem. It first runs GSA, followed by BAT as the second step. The proposed approach relies on a parameter between 0 and 1 to address the problem of falling into local research because the lack of a local search mechanism increases intensity search, whereas diversity remains high and easily falls into the local optimum. The improvement is equivalent to the speed of the original BAT. Access speed is increased for the best solution. All solutions in the population are updated before the end of the operation of the proposed algorithm. The diversification f

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Publication Date
Tue Feb 01 2005
Journal Name
Saudi Medical Journal
New intralesional therapy for basal cell carcinoma by 2% zinc sulphate solution
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KE Sharquie, AA Al-Nuaimy, FA Al-Shimary, Saudi medical journal, 2005 - Cited by 20

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Publication Date
Wed Mar 08 2017
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
New Schiff – Bases Prepared From Pyromellitic Dianhydride Via Its Hydrazide Derivative
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N, N′- bis[4-hydroxy phenyl] pyromillitdiimide [II] was prepared from the corresponding diamic acid , which was transfered to its new ester by the reaction with chloroethyl acetate [III ], [III] was used to prepare the novel hydrazide derivative [IV] , which was allowed to react with several aldehydes to yield the hydrazones [V – IX]. All the new compounds were synthesized , and characterized by their melting points .HNMR for some of them1FTIR,C,H,N analysis and ,

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Publication Date
Tue Mar 01 2016
Journal Name
International Journal Of Engineering Research And Advanced Technology (ijerat)
Speeding Up Back-Propagation Learning (SUBPL) Algorithm: A New Modified Back_Propagation Algorithm
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The convergence speed is the most important feature of Back-Propagation (BP) algorithm. A lot of improvements were proposed to this algorithm since its presentation, in order to speed up the convergence phase. In this paper, a new modified BP algorithm called Speeding up Back-Propagation Learning (SUBPL) algorithm is proposed and compared to the standard BP. Different data sets were implemented and experimented to verify the improvement in SUBPL.

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Publication Date
Mon Dec 20 2021
Journal Name
Bulletin Of The Iraq Natural History Museum (p-issn: 1017-8678 , E-issn: 2311-9799)
NEW RECORD OF THE GENUS LARRA FABRICIUS, 1793 (HYMENOPTERA, CRABRONIDAE) FROM VIETNAM
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The genus Larra Fabricius, 1793 (Hymenoptera: Crabronidae) is recorded for the first time from Vietnam. Three species and two subspecies belonging to this genus as follows: L. amplipennis (F. Smith, 1873); L. carbonaria (F. Smith, 1858); L. fenchihuensis Tsuneki, 1967; L. polita polita (F. Smith, 1858) and L. polita luzonensis Rohwer, 1919 are presented. Keys to both sexes of the three species and two subspecies reported here are provided.

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