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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
Mon Jan 01 2018
Journal Name
Al-mustansiriyah Journal Of Science
Relationship of Obesity to Serum Ferritin, Lipid Profile, uric acid and urea at Obesity Medical Center in Iraq
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Publication Date
Wed Dec 18 2019
Journal Name
Baghdad Science Journal
Spectrophotometric Determination of Mesalazine in Pharmaceutical Preparations by Oxidative Coupling Reactions with m-Aminophenol and 2,6- Dihydroxybenzoic Acid
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     Tow simple, rapid and sensitive spectrophotometric methods for the determination of mesalazine in pharmaceutical preparations have been carried out. The proposed methods depend on oxidative coupling reaction of mesalazine with m-aminophenol in the existence of N-bromosuccinamide in alkaline medium (method A) and 2,6-dihydroxybenzoic acid in the existence of sodium metaperiodate in basic medium (method B) to produce colored products , show highest absorptions at 640 (nm) and 515 (nm), alternately. Beer’s law was consistent in concentrations extent of 1.25-30 and 0.5-12.5 (µg.mL-1) with molar absorptivity of 0.36×104 and 0.77×104 L.mol-1.cm<

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Publication Date
Tue Mar 30 2021
Journal Name
Iraqi Journal Of Science
Evaluation of the Surveillance and Epidemiological Aspects of Cutaneous Leishmaniasis in Babylon Province, Iraq
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Leishmaniasis diseases constitute an important public health problem in both tropical and subtropical areas. The aim of this study is to evaluate the epidemiological situation of cutaneous leishmaniasis (CL) in Babylon province, Iraq. The current work included the recording of 142 new cases of CL infection in Babylon province for the period from November 2019 to February 2020. Male infection was represented by 87 cases (61.27%), while females composed 55 samples (38.73%), with a significant difference (p<0.05) between the two groups. The age group of 5-14 years was found to have the highest recorded CL cases  (56; 39.44%), while the age group of less than one year had the lowest  cases  (1; 0.70%), with the differences

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Publication Date
Wed Dec 26 2018
Journal Name
Iraqi Journal Of Science
Hydrochemical Evaluation and Utilization of Groundwater in Khanaqin Area, Diyala Governorate - East of Iraq
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The groundwater evaluation has been carried out in Khanaqin area in Diyala governorate to the east of Iraq. The analyzed hydrochemical parameters such as pH, electrical conductivity, total dissolved solids as well as cations and anions are used to describe groundwater quality and its suitability for different purposes. The study area covers (1920) km2. According to hydrogeological investigation (43) water points were inventoried and water levels in wells were measured. (34) Wells were sampled during 2013-2014 during water surplus and water deficit periods. The studied area is divided groundwater aquifers into two main units, the unconfined and confined aquifers. The values of pH, electrical conductivity (EC) and total dissolve

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Publication Date
Sun Sep 01 2019
Journal Name
Baghdad Science Journal
Evaluation of Physical Chemical and Biological Characteristics of Underground Wells in Badra City, Iraq
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The quality of groundwater should be improved by keeping safe water sources from contaminants in protective way by doing regular measuring and checkup before it supplied for usage. Private Wells do not receive the same services that wells supplying the public do. Well owners are responsible for protecting their drinking water. This work was carried out in Badra city, Iraq from December 2017 to May 2018, six wells water were investigated to determine the general characteristics of wells as well as studying the effect of environmental factors on the quality of water. The average of six wells were eleven parameters that is out of permissible limits were EC, Sal., Alk., TH, TDS, Na, Ca, Cl, SO4, Fe, Zn (4402-5183 /cm, 2.76-3.9 ppt

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Publication Date
Thu Mar 03 2022
Journal Name
Archives Of Rheumatology
Association of tumor necrosis factor-alpha promoter region gene polymorphism at positions -308G/A, -857C/T, and -863C/A with etanercept response in Iraqi rheumatoid arthritis patients
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Objectives: This study aims to evaluate the association between polymorphisms in the promoter region of the tumor necrosis factor-alpha (TNF-α) gene at locations -308G/A, -857C/T, and -863C/A with the tendency of being non-responder to etanercept.

Patients and methods: Between October 2020 and August 2021, a total of 80 patients (10 males, 70 females; mean age: 50 years; range, 30 to 72 years) with rheumatoid arthritis (RA) receiving etanercept for at least six months were included. The patients were divided into two groups responders and non-responders, based on their response after six months of continuous treatment. Following polymerase chain reac

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Publication Date
Thu Sep 30 2010
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
PREDICTION OF FINITE CONCENTRATIONBEHAVIOR FROM INFINITE DILUTION EGUILIBRIUM DATA
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Experimental activity coefficients at infinite dilution are particularly useful for calculating the parameters needed in an expression for the excess Gibbs energy. If reliable values of γ∞1 and γ∞2 are available, either from direct experiment or from a correlation, it is possible to predict the composition of the azeotrope and vapor-liquid equilibrium over the entire range of composition. These can be used to evaluate two adjustable constants in any desired expression for G E. In this study MOSCED model and SPACE model are two different methods were used to calculate γ∞1 and γ∞2

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Publication Date
Tue Sep 03 2019
Journal Name
Eastern-european Journal Of Enterprise Technologies
Prediction of spot welding parameters using fuzzy logic controlling
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Publication Date
Mon Oct 29 2018
Journal Name
International Journal Of Women's Health And Reproduction Sciences
Prediction of Placenta Accreta Using Hyperglycosylated Human Chorionic Gonadotropin
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Objectives: Hyperglycosylated human chorionic gonadotropin (hCG) is a variant of hCG. In addition, it has a different oligosaccharide structure compared to the regular hCG and promotes the invasion and differentiation of peripheral cytotrophoblast. This study aimed to measure hyperglycosylated hCG as a predictor in the diagnosis of placenta accreta. Materials and Methods: In general, 90 pregnant women were involved in this case-control study among which, 30 ladies (control group) were pregnant within the gestational age of ≥36 weeks with at least one previous caesarean section and a normal sited placenta in transabdominal ultrasound (TAU). The other 60 pregnant women (case

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Publication Date
Fri Apr 01 2022
Journal Name
Civil Engineering Journal
Prediction of Urban Spatial Changes Pattern Using Markov Chain
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Urban land uses of all kinds are the constituent elements of the urban spatial structure. Because of the influence of economic and social factors, cities in general are characterized by the dynamic state of their elements over time. Urban functions occur in a certain way with different spatial patterns. Hence, urban planners and the relevant urban management teams should understand the future spatial pattern of these changes by resorting to quantitative models in spatial planning. This is to ensure that future predictions are made with a high level of accuracy so that appropriate strategies can be used to address the problems arising from such changes. The Markov chain method is one of the quantitative models used in spatial planning to ana

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