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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 Feb 01 2021
Journal Name
Materials Science Forum
The Feasibility of Using Micro Silica Sand Powder as Partial Replacement of Cement in Production of Roller Compacted Concrete
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Roller compacted concrete (RCC) is a special type of concrete with zero or even negative slump consistency. In this work, it had aimed to produce an RCC mix suitable for roads paving with minimum cost and better engineering properties so, different RCC mixes had prepared i.e. (M1, M2, M3, and M4) using specified percentages of micro natural silica sand powder (SSP) as partial replacement of (0%, 5%, 10%, and 20%) by weight of sulfate resistant Portland cement. Additionally, M-sand, crushed stone, filler, and water had been used. The results had obtained after 28 days of water curing. The control mix (M1) had satisfied the required f ‘c with accepted results for the other tests. M2 mix with SSP of 5% had

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Publication Date
Sun Mar 01 2015
Journal Name
Baghdad Science Journal
Variation of Faba Beans (Vicia faba L.) Traits Induced By Heat, Electric Shock and Mutagen Nitrous Acid
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This research was carried out to determine the impact of heat shock, electric shock and seeds in soaking nitrous acid mutagen solution on three cultivars of faba beans plant (Zaina, Aguadulce and Local) at the year 2012-2013. Factorial experiment was arranged in randomized complete block design (RCBD) with three replicates were used. The results showed that heat shock lead to early plants of 50% in flowering and an increase in the number of branches/plant and the number of seeds/pod compared to other treatments, whereas the seeds soaked in nitrous acid mutagen solution gave the highest plant height, leaf area index, number of pods/plant, seed weight, seed yield kg/ha, and did not differ significantly with treatment of electric shock in the

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Publication Date
Wed Nov 01 2023
Journal Name
Journal Of Ecological Engineering
Product Concentration, Yield Percentage and Productivity of Citric Acid Formation Using Aspergillus Niger Isolated from Palm Dates
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Publication Date
Wed Mar 01 2023
Journal Name
Journal Of Photochemistry And Photobiology A: Chemistry
Improved photocatalytic degradation of methyl violet dye and pathogenic bacteria using g-C3N4 supported phosphotungstic acid heterojunction
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Publication Date
Fri Jan 01 2010
Journal Name
Iraqi Journal Of Science
IMMUNONOLOGICAL EVALUATION AND ACUTE TOXICITY STUDY WITH FERTILITY EXAMINATION FOR THE EFFECT OF AQUEOUS EXTRACT FROM DRIED FRUITS OF Piper nigrum L. IN MICE
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The research work was conducted to investigate the effect of oral administration of water extract of black pepper at doses of (1, 5) mg/kg body weight for two weeks daily by determining the genotoxic effect (mitotic index), evaluation of immunological effect (IgG, IgM, IgA, C3, C4) and measuring fertility hormones (follicles stimulation hormone/FSH, lutenising hormone/LH) levels with histopathological examinations of female albino swiss mice ovaries in comparison with control (normal saline). A clear effect in increasing mitotic activity was reveled for both doses in comparison with control. Results also showed a significant increase in the value of the all immunological parameters at both doses in comparison with control. Also obvious rais

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Publication Date
Sun Jun 27 2021
Journal Name
Iraqi National Journal Of Nursing Specialties
Evaluation of Post-operative Nursing Care of Psychological Support and Discharge Plan for Women Undergone Hysterectomy at Maternity Wards in Baghdad City's Teaching Hospitals
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Objective: The study aims at evaluating the psychological support and discharge plan from the hospital provided by nurses for woman undergone hysterectomy.
Methodology: The study uses descriptive design and non-probability (convenient) sample which is consisted of (40) nurses from (8) teaching hospitals in the City of Baghdad within the maternity wards. The study is carried out from 11 November 2020 to 27 June 2021. A observational tool is developed to evaluate the psychological support and the discharge plan after surgery. Content validity and internal consistency reliability are determined through pilot study. Data are collected through the use of the questionnaire and data are analyzed through the use of descriptive and inferentia

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Publication Date
Wed Jun 01 2016
Journal Name
Journal Of Economics And Administrative Sciences
Performance evaluation of small and medium-sized enterprises according to the entrance of the scorecard applied study in company Al fadly for construction industries
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The research Aim is to provide support to small enterprises by providing tools that enable measurement and test their performance and identifying weaknesses and work on them is determined by the problem of searching using traditional assessment methods for small projects with only financial performance measurement standards that do not provide a complete picture of the performance of these projects so use the balanced scorecard the four pillars (financial, customer, learning and growth, and internal processes) and identify deviations and work on them through the use of the outputs of the programme (probe), PROmoting Business Excellence-PROBE), which It is a model of performance evaluation, with which you can deve

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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)
Preparation and Evaluation of Liquid and Solid Self-Microemulsifying Drug Delivery System of Mebendazole
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The aim of present study was to develop solid and liquid  self-microemulsifying drug  delivery system of poorly water soluble drug mebendazole using Aerosil 200 as solid carrier.  Microemulsions are clear, stable, isotropic liquid mixtures of oil, water and surfactant, frequently in combination with a co-surfactant having droplet size range usually in the range of 20-250 nm. Oleic acid, tween 80 and polypropylene glycol were selected as oil, surfactant and co-surfactant respectively and for preparation of stable SMEDDS, micro emulsion region was identified by constructing pseudo ternary phase diagram containing different proportion of surfactant: co-surfactant (1:1, 2:1 and 3:1), oil and water. In brief S/ CoS mix means su

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Publication Date
Mon Aug 01 2022
Journal Name
Baghdad Science Journal
Lymphocytes Prediction of Homeostasis Model Assessment of Beta-cells Function (HOMA-B) and C-peptide Level during Pregnancy: New Insight into Beta-cells Proliferation and Insulin Sensitivity
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This work aims to detect the associations of C-peptide and the homeostasis model assessment of beta-cells function (HOMA2-B%) with inflammatory biomarkers in pregnant-women in comparison with non-pregnant women. Sera of 28 normal pregnant women at late pregnancy versus 27 matched age non-pregnant women (control), were used to estimate C-peptide, triiodothyronine (T3), and thyroxin (T4) by Enzyme-linked-immunosorbent assay (ELISA), fasting blood sugar (FBS) by automatic analyzer Biolis 24i, hematology-tests by hematology analyzer and the calculation of HOMA2-B% and homeostasis model assessment of insulin sensitivity (HOMA2-S%) by using C-peptide values instead of insulin. The comparisons, correlations, regression analysis tests were perfo

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Publication Date
Wed Dec 01 2021
Journal Name
Journal Of Economics And Administrative Sciences
Using Fuzzy Inference to Evaluation Suppliers in Diyala General Electric Industries Company
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The research aims to evaluate the suppliers at Diyala general electric industries company conducted in an environment of uncertainty and fuzzy where there is no particular system followed by the company, and also aims to use the problem of traveling salesman problem in the process of transporting raw materials from suppliers to the company in a fuzzy environment. Therefore, a system based on mathematical methods and quantity was developed to evaluate the suppliers. Fuzzy inference system (FIS) and fuzzy set theory were used to solve this problem through (Matlab) and the problem of the traveling salesman in two stages was also solved by the first stage of eliminating the fuzzing of the environment using the rank function method, w

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