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Synthesis, In Silico Prediction, and In Vitro Evaluation of Anti-tumor Activities of Novel 4'-Hydroxybiphenyl-4-carboxylic Acid Derivatives as EGFR Allosteric Site Inhibitors
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Introduction:

Allosteric inhibition of EGFR tyrosine kinase (TK) is currently among the most attractive approaches for designing and developing anti-cancer drugs to avoid chemoresistance exhibited by clinically approved ATP-competitive inhibitors. The current work aimed to synthesize new biphenyl-containing derivatives that were predicted to act as EGFR TK allosteric site inhibitors based on molecular docking studies.

Methods:

A new series of 4'-hydroxybiphenyl-4-carboxylic acid derivatives, including hydrazine-1-carbothioamide (S3-S6) and 1,2,4-triazole (S7-S10) derivatives, were synthesized and characterized using IR, 1HNMR, 13CNMR, and HR-mass spectroscopy.

Results:

Compound S4 had a relatively high pharmacophore-fit score, indicating that it may have biological activity similar to the EGFR allosteric inhibitor reference, and it scored a relatively low ΔG against EGFR TK allosteric site, indicating a high likelihood of drug-receptor complex formation. Compound S4 was cytotoxic to the three cancer cell lines tested, particularly HCT-116 colorectal cancer cells, with an IC50 value comparable to Erlotinib. Compound S4 induced the intrinsic apoptotic pathway in HCT-116 cells by arresting them in the G2/M phase. All of the new derivatives, including S4, met the in silico requirements for EGFR allosteric inhibitory activity.

Conclusion:

Compound S4 is a promising EGFR tyrosine kinase allosteric inhibitor that warrants further research.

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Publication Date
Wed Sep 14 2016
Journal Name
Journal Of Baghdad College Of Dentistry
A Comparative Evaluation of Apical Seal Associated with Ultrasonic Retrograde Cavities Filled with Bioactive Material (In Vitro Study)
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Background: The aim of this study was to evaluate and compare the apical microleakage around retrograde cavities prepared with ultrasonic technique and filled with (Biodentineâ„¢) Materials and methods: 40 extracted single rooted human permanent maxillary teeth with mature apices were selected. The roots were prepared chemo-mechanically using k-files with crown-down technique and then obturated with lateral condensation gutta-percha technique. Teeth were divided into four main groups according to the cavity preparation method either manual or ultrasonic technique: Group A (n=10): A class I retrograde cavity at root end was prepared with traditional handpeice equipped and placement of Biodentine with manual condensation. Group B (n=10):

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Publication Date
Fri Jan 01 2016
Journal Name
Journal Of Baghdad College Of Dentistry
A Comparative Evaluation of Apical Seal Associated with Ultrasonic Retrograde Cavities Filled with Bioactive Material ( in Vitro Study )
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Background: The aim of this study was to evaluate and compare the apical microleakage around retrograde cavities prepared with ultrasonic technique and filled with (Biodentineâ„¢) Materials and methods: 40 extracted single rooted human permanent maxillary teeth with mature apices were selected. The roots were prepared chemo-mechanically using k-files with crown-down technique and then obturated with lateral condensation gutta-percha technique. Teeth were divided into four main groups according to the cavity preparation method either manual or ultrasonic technique: Group A (n=10): A class I retrograde cavity at root end was prepared with traditional handpeice equipped and placement of Biodentine with manual condensation. Group B (n=10):

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Publication Date
Tue Mar 28 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Study the Effect of Folic Acid as A supplement on Selected Oxidative Stress and Biochemical Parameters in First Trimester of Pregnancy
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Folic acid modulates several disorders in humans, pregnancy mostly because of the mitochondria-rich placenta, is a condition that favors oxidative stress.Transitional metals, especially iron, which are particularly abundant in the placenta, are important in the production of free radicals. Adenosine deaminase (ADA), an enzyme essential for the differentiation of lymphoid cells, has been used for monitoring diseases with altered immunity. In the present study we investigated the effect of regular and irregular administered folic acid in the first and second trimester of pregnancy to be compared with non-pregnant women ,and also the effect of regular and irregular using of folic acid  supplement on  oxidative stress parameters an

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Publication Date
Fri Jul 19 2024
Journal Name
Baghdad Science Journal
Synthesis, Characterization, and Thermal Studying of VO(II), Cu(II), Zn (II), Cd(II), and Au (III) Complexes with Azo Dye and Evaluation as Antioxidants
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حضرت معقدات كل من الفنادايل, الخارصين, النحاس والكادميوم بتكافؤهم الثنائي والذهب بتكافؤه الثلاثي بأستخدام صبغة ازوجديدة (6،4،2-ثلاثي هيدروكسي-3-((3-هيدروكسي فنيل) ثنائي زينيل ) فنيل ) ايثان-1-اون المحضرة من ملح الديازونيوم مع ٦,٤,٢- ثلاثي هيدروكسي اسيتوفينون بعد عزل (E)-1-(2,4,6-trihydroxy-3-((3-hydroxyphenyl)diazenyl)phenyl)ethan-1-one تم تشخيصها بواسطة الطرق الطيفية المتاحة  والتقنيات التشخيصية لكل من التحليل الدقيق للعناصرواطياف كل من ال

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Publication Date
Wed Mar 18 2020
Journal Name
Baghdad Science Journal
Spectrophotometric and Reverse Flow Injection Method Determination of Nitrazepam in Pharmaceuticals Using O-Coumaric Acid as a New Chromogenic Reagent
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            A spectrophotometric- reverse flow injection analysis (rFIA) method has been proposed for the   determination of Nitrazepam (NIT) in pure and pharmaceutical preparations. The method is based upon the coupling reaction of NIT with a new reagent O-Coumaric acid (OCA) in the presence of sodium periodate in an aqueous solution. The blue color product was measured at 632 nm. The variation (chemical and physical parameters) related with reverse flow system were estimated. The linearity was over the range 15 - 450 µg/mL of NIT with detection limits and limit of quantification of 3.425 and 11.417 µg mL-1 NIT,respectively. The sample throughput of 28 samples

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Publication Date
Wed Jun 12 2019
Journal Name
Journal Of Global Pharma Technology
Age Gender and Site Effect on Immunohistochemical Expression of TGF-β1 and IFN-γ in Hereditary Gingival Fibromatosis
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Publication Date
Sun Mar 06 2016
Journal Name
Baghdad Science Journal
Synthesis and Characterization of Some New Azo Dyes Derivatives Via Chalcone and Study Some of Their Biological Activity
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This work includes synthesis of new six membered heterocyclic rings with effective amino group using the reaction of benzylideneacetophenone (chalcone) (1) with thiourea or urea in alcoholic basic medium to form: 1,3-thiazen-2-amine (2), and 1,3-oxazin-2-amine (8) respectively. The diazotization reaction was carried out with sodium nitrite in presence of hydrochloric acid to form diazonium salts which suffered coupling reaction with naphthols and phenols in the presence of sodium hydroxide to form colored azo dyes (4-7, and 10-13). o-methylation reaction of compounds (7) and (10) yielded : 1,3-thiazin -2-yl-diazenyl (14), and 1,3-oxazin-2-yl-diazenyl (15) respectively.The new compounds were characterized using vario

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Publication Date
Sat Sep 23 2017
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
Synthesis and Characterisation of Novel Cobalt(li),Copper (II) and Mercury (II) Complexes of Poly Vinyl Urethanised Oxime.
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The reaction  of poly (vinyl  alcohol) (PV A) with Urea in (DMSO)

resulted  in uerthanised oxim, wr,ich reacted with diacetylmonoxime  in a (DY.ISOfmethanol) to give anew type (N2) polymeric bidentate imine oxime ligand [HL], The ligand was reacted with MCh (where M= Co, Cu, and Hg). Under  reflux in a (DMF/Methanol) mixture with (I:1) ratio to give Complexes  of the general formula [M (T.)2]X, (where M=

Co,Hg,  Cu). All .:ompouncs have been characterized  by spectroscopic

methods  [IR,  U.V.-Vis, A tomi<;absorption] microanalysis along with conductivity measurements, from  the  above::  data the proposed molecular structure for Co,Cu, and Hg is a

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Publication Date
Wed Mar 19 2008
Journal Name
Ibn Al-haitham Journal For Pure And Applied Science
Synthesis and Characterisation of Novel Cobalt (li), Copper (II) and Mercury (II) Complexes of Poly Vinyl Urethanised Oxime
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The reaction of poly (vinyl alcohol) (PV A) with Urea in (DMSO) resulted in uerthanised oxim, wr,ich reacted with diacetylmonoxime in a (DY.ISOfmethanol) to give anew type (N2) polymeric bidentate imine oxime ligand [HL], The ligand was reacted with MCh (where M= Co, Cu, and Hg). Under reflux in a (DMF/Methanol) mixture with (I:1) ratio to give Complexes of the general formula [M (T.)2]X, (where M= Co,Hg, Cu). All .:ompouncs have been characterized by spectroscopic methods [IR, U.V.-Vis, A tomi<;absorption] microanalysis along with conductivity measurements, from the above:: data the proposed molecular structure for Co,Cu, and Hg is a distorted. Tetrahedml

Publication Date
Thu Dec 19 2019
Journal Name
Opcion Journal
The Role of Agricultural Activities in Achieving Sustainable Development
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Agricultural development occupies an important position in the economies of developing countries, and its role is greater for the Arab countries. The first task is to provide food security for all the population through sustainable development, which includes the investment of available natural resources and employment opportunities for the rural population, As well as the provision of raw materials for agricultural processing in order to increase agricultural exports to reduce the balance of payments deficit. Sustainable development is linked to increased production and improvement, as well as to food security. On the one hand, it has to cope with the increase in population and if it is possible to achieve a surplus allocated for export, a

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