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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
Tue Jan 11 2022
Journal Name
Iraqi Journal Of Science
The Effect of Zinc oxide Nanoparticles (ZnO NPs) on the Viability of Leishmania tropic In Vitro
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Cutaneous leishmaniasis (CL) also known under local names like (tropical sore, oriental sore and Baghdad sore) is the most common form of leishmaniasis. It is a public health and a social problem in many developing countries. The Old World disease primarily is caused by Leishmania major in dry desert areas and Leishmania tropica in urban areas. Recently, metal oxide nanoparticales have been versatile platforms for biomedical applications and therapeutic interventions. There is an urgent need to develop new types of antileishmanial agents instead of classical drug (pentostam), especially, when its efficacy showed a decline towards some strains of Leishmania. Therefore, the present work was aimed to evaluating antileishmanial activity of z

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Publication Date
Tue Dec 13 2005
Journal Name
Iraqi Journal Of Laser
Stimulation of Phagocytic Activity of Human Polymorphonuclear Leukocytes in Vitro Using 10 mW He-Ne Laser.
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Stimulative effect of 10 mW He-Ne laser on the phagocytic activity of human polymorphonuclear leukocytes( PMNs) has been studied in vitro. Normal polymorphonuclear leucocytes were isolated from the human peripheral blood. A mixture of 0.25 ml of Hanks solution, 0.25 ml of serum, 0.25 ml of Candida albicans suspension and 0.25 ml of PMNs suspension was prepared. The samples of mixture of PMNs and Candida were subdivided in 1 ml ependrof tubes and irradiated to He-Ne laser for 1, 3, 5, 10 and 20 min. The diameter of the irradiated area was 0.8 cm. For calculation of Phagocytic index before and after irradiation, the samples were incubated (37°C) at 5, 15, 30, 60 min. The slides of samples were prepared and stained using Giemsa stain. The

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Publication Date
Sat Jun 06 2015
Journal Name
Advances In Life Science And Technology
Cytotoxic Effect of Aqueous Extract of Anastatica hierochuntica L. on AMN-3 Cell Line in vitro
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Anastatica hierochuntica L. is distributed throughout Arabain Peninsula, and elsewhere it is locally called "Kuffe Maryam" .All parts of the plant are used in folk medicine. This study amid to investigate the effect of aqueous extract of anastatica hierochunctica L. on the cancer cell lines AMN-3. Anti cancer activity of aqueous extract of anastatica hierochunctica L. showed anticancer activity against AMN-3 cell line for twelve concentrations (0.04, 0.09, 0.195, 0.39, 0.78, 1.56, 3.125, 6.25, 12.5, 25, 50, 100) mg/mL in comparison with negative control.

Publication Date
Wed Sep 14 2016
Journal Name
Journal Of Baghdad College Of Dentistry
Comparison of Shear Bond Strength of Three Different Brackets Bonded on Zirconium Surfaces (In Vitro Study)
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Background: With the increased in the demands of adult orthodontics, the challenge of direct bonding to non-enamel surface (zirconium) had been increased. The present study was carried out to compare the shear bond strength of three different brackets (stainless steel, sapphire and composite) bonded to zirconium surface and study the mode of bond failure. Materials and methods: The sample was comprised of 30 models (8mm *6mm*1.5mm) of full contour zirconium veneers. They were divided into three groups according to the brackets type; all samples were treated first by sandblast with aluminum oxide particle 50 µm then coated by z-prime plus primer. A central incisor bracket of each group was bonded to the prepared zirconium surface with lig

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Publication Date
Wed Feb 05 2025
Journal Name
Journal Of Baghdad College Of Dentistry
Effect of zinc oxide nanoparticles on total salivary peroxidase activity of human saliva (In vitro study)
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Background: The potential use of zinc oxide and other metal oxide nanoparticles in biomedical are gaining interest in the scientific and medical communities, largely due to the physical and chemical properties of these nanomaterials. The present work revealed the effect of zinc oxide nanoparticles (ZnONPs) on the total salivary peroxidase enzyme activity of human saliva in comparison to de-ionized water. Materials and methods: Forty eight unstimulated saliva samples were collected from dental students/University of Baghdad 18-22 years. Then measure the total salivary peroxidase activity first without any addition to human saliva as a control, second with dilution the saliva with de-ionized water, and third with zinc oxide nanoparticles in c

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Publication Date
Mon Dec 25 2017
Journal Name
Al-khwarizmi Engineering Journal
Prediction of Oxygen Mass Transfer Coefficients in Stirred Bioreactor with Rushton Turbine Impeller for Simulated (Non-Microbial) Medias
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 Abstract

The study of oxygen mass transfer was conducted in a laboratory scale 5 liter stirred bioreactor equipped with one Rushton turbine impeller. The effects of superficial gas velocity, impeller speed, power input and liquid viscosity on the oxygen mass transfer were considered. Air/ water and air/CMC systems were used as a liquid media for this study. The concentration of CMC was ranging from 0.5 to 3 w/v. The experimental results show that volumetric oxygen mass transfer coefficient increases with the increase in the superficial gas velocity and impeller speed and decreases with increasing liquid viscosity. The experimental results of kla were correlated with a mathematical correlation des

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Publication Date
Fri Jan 26 2024
Journal Name
Iraqi Journal Of Science
Evaluation of groundwater recharge in arid and semiarid regions (case study of Dibdiba formation in Karballa-Najaf plateau)
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The process of recharge the groundwater is the key factors that need to be addressed as is the foundation upon which the process of groundwater use and management properly, especially in arid and semi-arid, like Iraq, so the values of groundwater recharge calculated vary depending on the method used in the calculation and the more factors calculated in the process of calculating the values of groundwater recharge increased margin of error in these values. In this study were selected four methods to calculate the value of recharge for groundwater (fluctuating water table, water balance of the basin, numerical modeling, and balance of chloride ion mass in unsaturated zone) was applied in the Plateau area of Karbala (Dibdiba formation) has

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Publication Date
Sun Feb 10 2019
Journal Name
Journal Of The College Of Education For Women
Woman’s Identity Crisis in the Clash of Cultures: A Study of Betool Khedairi’s Novel: A Sky So close
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This paper is an attempt to clarify the impact of Postcolonialism, one of the most
challenging fields of study that has emerged in recent years, on representations of women in
once-colonised countries and in Western locations. It discusses the influence of cultural
differences on the status and identity of a woman who experience ‗multiculturalism‘. The
study is an analytical reading of a contemporary novel written by the Iraqi writer Betool Al-
Kudairi. The emphasis lies on the clash between two different cultures and traditions
represented by the British mother and the Iraqi father and its effect on the life and identity of
the protagonist. The main focus is on idea of ‗hybrid identity‘ and the absence of th

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Publication Date
Sun Sep 06 2015
Journal Name
Baghdad Science Journal
Evaluation of the level of Some Heavy Metals in Tobacco of Domestic and Imported Cigarette Brands Used in Iraq
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Smoking-related diseases can be attributed to the inhalation of many different toxins, including heavy metals, which have a host of harmful health effects. The primary objective of this study was to determine whether local and imported cigarette brands used in Iraq , have they elevated levels of metals or not .Three metals Lead (Pb) , Cadmium (Cd) and Chromium(Cr) were determined in tobacco of seventeen brands of imported cigarettes commonly available in Iraq and three Iraqi domestic cigarettes , which were randomly taken from retail market in Baghdad by using flame atomic absorption spectrometry. The produced data of imported and local cigarette brands were discussed and compared together and with studies from elsewhere .The result

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Publication Date
Tue Jun 01 2021
Journal Name
International Journal Of Agricultural And Statistical Sciences
Effect of phosphorous and amino acid on growth and yield of pea
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