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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
Thu Mar 30 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
In Vitro Effect of Cholesterol and Different Sugars on Digitonin Production in Multiplied Shoots of Digitalis purpurea L. Plant
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Production of  the steroidal saponin digitonin  in multiplied shoots of Digitalis purpurea , (var. Excelsior Mixed) has been achieved in vitro by two experiments. In the experiment 1, shoot tips ( 1cm length ) explants  from the sterilized seedlings were excised and cultured on MS medium ( Murashige and Skoog medium) supplemented with 0.5 mg/L TDZ (thidiazuron) and   cholesterol at the concentrations 0.0, 0.1, 0.3, 0.5, 1.0, 1.5, 2.0 or 4.0 mg/L. After 45 day, results showed that the treatment with 0.5 mg/L TDZ and 2.0mg/L cholesterol had a positive effected on increasing the dry weight of multiplied shoots and their production of digitonin when compared with other treatments, where this treatment gave 2

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Publication Date
Sun Feb 03 2019
Journal Name
Journal Of The College Of Education For Women
Aljdhiran incision and rip and derivatives in the Qur'an: A statistical study morphological tag
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It is more beneficial science and created and the highest honor is the Koran Sciences, God has honored research in this fun science, came this research that shed the light on the radical incision, and Naughty derivatives as contained in the Koran, and illustrate the diversity of Saghma morphological, and fork them from derivatives what it entailed connotations, as well as the evacuation of cryptic in some of these verses from the biological secrets take minds newly exposed Anitrjt science under the name of scientific miracles.
The research methodology is revenue verse which included the word, and revenue lexical meaning and its meaning in the context of the Qur'an, and reflect the views of the commentators of the verse, and then the r

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Publication Date
Wed Aug 28 2019
Journal Name
International Journal Of Drug Delivery Technology
Synthesis, Characterization and Screening their Antibactrial Activity of some New Oxazepine and Diazepine Compounds Containing 1,3,4-Oxadiazole Ring Derived from L-Ascorbic Acid
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The search involve the synthesis of some new 1,3-oxazepine and 1,3-diazepine derivatives were synthesized from Schiff base. The Schiff base (VIII) prepared from reaction of aldehyde (IV) derived from L-ascorbic acid with aromatic amine ([2-(4- nitrophenyl)-5-(4-aminophenyl)-1,3,4-oxadiazole] (VII). Oxazepine compounds (IX-XI) were synthesized from the cyclic condensation of Schiff base (VIII) with (maleic, phthalic and 3-nitrophthalic) anhydride, compounds (IX-XI) that were reacted with p-methoxyaniline to give diazepine derivatives (XII-XIV). The structures of the new synthesized compounds have been confirmed by physical properties and spectroscopy measurements such as FTIR, and some of them by 1 H-NMR, 13 CNMR, Mass, and evaluated

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Publication Date
Sun Jun 20 2021
Journal Name
Bulletin Of The Iraq Natural History Museum (p-issn: 1017-8678 , E-issn: 2311-9799)
PETROLOGY AND PROVENANCE OF THE NATURAL STONE TOOLS FROM Al-DALMAJ ARCHAEOLOGICAL SITE, MESOPOTAMIAN PLAIN, IRAQ
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Many stone tools were found on a hill south of the Hor Al-Dalmaj which is located in the central part of the alluvial plain of Mesopotamia, between the Tigris and Euphrates Rivers. The types of rocks from which the studied stone tools were made are not found in the alluvial plain, because it consists of friable sand, silt, and clay. All existing sediments were precipitated in riverine environments such as point bar, over bank, and floodplain sediments. The collected stone tools were described with a magnifying glass (10 x) and a polarized microscope after they were thin sectioned. Microscopic analysis showed that these stone tools are made of sedimentary, volcanic igneous and metamorphic rocks, such as: sandstones, limestones, chert, con

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Publication Date
Mon Aug 17 2020
Journal Name
Systematic Reviews In Pharmacy
New mixed ligand complexes of New Schiff base 4,4'- ((naphthalen-1-ylimino) methylene) dibenzene-1,3-diol and 8-hydroxy quinoline: Synthesis, Spectral Characterization, Thermal studies and Biological Activities
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New mixed ligand complexes of New Schiff base 4,4'- ((naphthalen-1-ylimino) methylene) dibenzene-1,3-diol and 8-hydroxy quinoline: Synthesis, Spectral Characterization, Thermal studies and Biological Activities

Publication Date
Tue Oct 02 2018
Journal Name
Iraqi Journal Of Physics
Measurement of indoor radon levels and assessment of radiological hazards at Al-Tuwaitha nuclear site and the surrounding area
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In the present study the radon concentration was measured in indoor places by the RAD7 (radon detector) was in some locations at Al-Tuwaitha nuclear site and some surrounding areas for the duration from 13/10/2016 to 2/1/2017 and the measurement of the indoor radon concentration ranged from (4.96±4.4 to 102±25) Bq/m3. The high value of radon has been found at decommissioning directorate /emergency room, which is lower than the action value recommended by the Environmental Protection Agency (EPA) which is (148 Bq/m3) while the lowest value has been founded in central laboratories directorate \ models room. These values were used to calculate the annual effective dose and the health risks for cells bronchial which caused by the inhalatio

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Publication Date
Fri Sep 21 2012
Journal Name
Open Journal Of Obstetrics And Gynecology
Evaluation of thalamus echogenicity by ultrasound as a marker of fetal lung maturity
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Publication Date
Sun Dec 17 2017
Journal Name
Al-khwarizmi Engineering Journal
Experimental and Prediction Using Artificial Neural Network of Bed Porosity and Solid Holdup in Viscous 3-Phase Inverse Fluidization
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In the present investigation, bed porosity and solid holdup in viscous three-phase inverse fluidized bed (TPIFB) are determined for aqueous solutions of carboxy methyl cellulose (CMC) system using polyethylene and polypropylene as  a particles with low-density and diameter (5 mm) in a (9.2 cm) inner diameter with height (200 cm) of vertical perspex column. The effectiveness of gas velocity Ug , liquid velocity UL, liquid viscosity μL, and particle density ρs on bed porosity BP and solid holdups εg were determined. The bed porosity increases with "increasing gas velocity", "liquid velocity", and "liquid viscosity". Solid holdup decreases with increasing gas, liquid

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Publication Date
Fri Nov 01 2019
Journal Name
Journal Of Engineering
Prediction of Heat Transfer Coefficient and Pressure Drop in Wire Heat Exchanger Working with R-134a and R-600a
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An experimental and theoretical works were carried out to model the wire condenser in the domestic refrigerator by calculating the heat transfer coefficient and pressure drop and finding the optimum performance. The two methods were used for calculation, zone method, and an integral method. The work was conducted by using two wire condensers with equal length but different in tube diameters, two refrigerants, R-134a and R-600a, and two different compressors matching the refrigerant type. In the experimental work, the optimum charge was found for the refrigerator according to ASHRAE recommendation. Then, the tests were done at 32˚C ambient temperature in a closed room with dimension (2m*2m*3m). The results showed that th

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Publication Date
Wed Jan 24 2024
Journal Name
Al-rafidain Journal Of Medical Sciences ( Issn 2789-3219 )
Development and Characterization of Hyaluronic Acid-Incorporated Thermosensitive Nasal in situ Gel of Meclizine Hydrochloride
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Background: Meclizine hydrochloride (MCZ) is an antihistamine that is used as an antiemetic to prevent and cure nausea and vomiting. Because of its limited water solubility and first-pass metabolism, it exhibits variable absorption. Objective: To formulate and evaluate MCZ as an intranasal in situ gel with increased residence time and permeability. Methods: We made an inclusion complex of MCZ using various cyclodextrins as a complexing agent to help the drug dissolve better. The complexes were studied, and the ones that were better at dissolving were chosen to be used in the creation of an in situ gel with poloxamer 407 (17–20% w/v) and hyaluronic acid (0.25–0.75% w/v). Prepared formulas were subjected to various evaluation tes

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