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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 Dec 09 2015
Journal Name
Iraqi Journal Of Market Research And Consumer Protection
Effect of Sodium sulfite treatment on the trypsin inhibitors activity, protein isolate and protein solubility of complete and dehulling white bean seeds Phaseolus vulgaris.: Effect of Sodium sulfite treatment on the trypsin inhibitors activity, protein isolate and protein solubility of complete and dehulling white bean seeds Phaseolus vulgaris.
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The study aimed to increase the biological value of white bean. The effect of different concentrations 0.01 ,0.02,0.03,and 0.04 M of sodium sulfite solutions for 1hr at 70 ºC on the trypsin inhibitors activity, protein isolate and protein solubility of complete and dehulling white bean flour were studied.Trypsin inhibitors activity were reduced by 42.97, 58.69, 68.59 and 69.58% in complete white bean flour at 0.01 ,0.02, 0.03, 0.04 M respectively, while the corresponding values were 50.43, 61.00, 75.61 and 85.66% respectively in dehulling white bean flour .Protein isolate value was 13.41% and protein solubility was 2.2% in control sample, Furthermore, the using of chemical treatment showed that protein isolate was reduced gradually and

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Publication Date
Sun Jun 05 2016
Journal Name
Baghdad Science Journal
Effect of different concentration of Gibberellic and Proline acid in the growth and production of pea plant Pisum sativum L.
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This experiment was conducted to evaluate the effect of foliar spraying with gibberellic acid concentrations (0,50,100)mg.L­¹ and proline acid concentrations (0, 25, 50)mg.L­¹ and their interactions on some growth parameters of pea plant using clay pots in the botanical garden of Biology Department College of Education for pure science Ibn –Al-Haitham ,Baghdad University, for the growing season 2012-2013 the experiment involved the studing of some growth parameters as plant?s height, dry weight, wt. of pods.plant­¹, biology yield and the concentration of some major elements (nitrogen, phosphorus and calcium) in plant?s seeds. The experiment was designed according to Completely Randomized Desig(CRD) with three replications. R

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Publication Date
Mon Dec 11 2017
Journal Name
Al-khwarizmi Engineering Journal
Improvement of Mechanical and Rheological Properties of Natural Rubber for Anti-Vibration Applications
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Abstract  

This research aims to study and improve the passivating specifications of rubber resistant to  vibration. In this paper, seven different rubber recipes were prepared based on mixtures of natural rubber(NR)  as an essential part in addition to the synthetic rubber (IIR, BRcis, SBR, CR)with different rates. Mechanical tests such as tensile strength, hardness, friction, resistance to compression, fatigue and creep testing in addition to the rheological test were performed. Furthermore, scanning electron microscopy (SEM)test was used to examine the structure morphology of rubber. After studying and analyzing the results, we found that, recipe containing (BRcis) of 40% from th

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Publication Date
Thu Sep 03 2020
Journal Name
Al-kindy College Medical Journal
Unusual Location of Giant Cell Tumor of the Tendon Sheath .. A Case Report
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Locking of the knee is a one of the commonest orthopedic outpatient presentation. This patient usually need magnetic resonance imaging (MRI) when there is suspected lesion in the soft tissue clinically. Meniscal tears is the first differential diagnosis when accompany with painful knee. (1, 2)Giant cell tumor (GCT) is benign a localized nodular tenosynovitis often occur in the tendon sheath , Mostly involve the hand tendons in middle age group between 30 and 50 years old , female affect more than male.(3,4) The WHO defines two well-known kinds of giant cell tumor: (1) pigmented villonodular synovitis ( generalized type), which mainly involve the joints of the lower limb and (2) giant cell tumor of the tendon sheath ( localized type)

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Publication Date
Thu Sep 03 2020
Journal Name
Al-kindy College Medical Journal
Unusual Location of Giant Cell Tumor of the Tendon Sheath .. A Case Report
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Locking of the knee is a one of the commonest orthopedic outpatient presentation. This patient usually need magnetic resonance imaging (MRI) when there is suspected lesion in the soft tissue clinically. Meniscal tears is the first differential diagnosis when accompany with painful knee. (1, 2)
Giant cell tumor (GCT) is benign a localized nodular tenosynovitis often occur in the tendon sheath , Mostly involve the hand tendons in middle age group between 30 and 50 years old , female affect more than male.(3,4) The WHO defines two well-known kinds of giant cell tumor: (1) pigmented villonodular synovitis ( generalized type), which mainly involve the joints of the lower limb and (2) giant cell tumor of the tendon sheath ( localized type)

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Publication Date
Fri Dec 27 2024
Journal Name
Epitheorese Klinikes Farmakologias Kai Farmakokinetikes – Greek Edition
Response surface optimization and in vitro study of nasal solusomes nanovesicles for the bioavailability improvement and brain targetting of sumatriptan
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Background: One effective second-generation triptan for migraine attacks is sumatriptan. Following oral use, it has a 40% restricted bioavailability because of the first-pass metabolism. Aim: To develop the best intranasal Solusomes formula as a substitute that delivers into the brain directly, improving its bioavailability, and removing the first-pass outcome was the aim of this effort. Methodology: We developed solute formulations based on the Box-Behnken design and subsequently produced them via thin-film hydration. The quality by design technique was used to establish a correlation between the formulation parameters (Soluplus® and phosphatidylcholine (PC) concentrations) and signif¬icant quality powers (entrapment efficiency (

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Publication Date
Sun Dec 25 2022
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Quantitative Determination and Cytotoxic Effect of Oleanolic Acid from Olea europaea Leaves Extract Cultivated in Iraq
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Since its first description as a cytotoxic agent, Olea europaea leaves extract gained significant popularity against human breast cancer, ethyl acetate extract of Olea europaea leaves obtained by acid hydrolysis method was evaluated in vitro as cytotoxic agent against new human breast cancer (AMJ13) cell line, using the MTT assay. One main pentacyclic triterpenoid; oleanolic acid, was isolated from leaves of Olea europaea by well-known two different methods, but not used for this compound before, the acidic hydrolysis method and basic acidic method. The presence of oleanolic acid was proved in both methods with qualitative and quantitative d

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Publication Date
Fri Dec 27 2024
Journal Name
International Journal Of Design & Nature And Ecodynamics
Amino Acid and Hormonal Profiling of the Adrenal Gland in the Pin-Tailed Sandgrouse (Pterocles alchata)
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Publication Date
Tue Jan 01 2019
Journal Name
Iraqi Journal Of Agricultural Sciences
Effect of magnetic field on the growth, multiplication and concentration of the volatile oil of rosemary officinalis in vitro
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Publication Date
Mon Jul 31 2023
Journal Name
International Journal Of Sustainable Development And Planning
Monitoring and Prediction Functional Change of Land Uses Toward Urban Sustainability
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Urban land uses are in a dynamic state that varies over time, the city of Karbala in Iraq has experienced functional changes over the past 100 years, as the city is characterized by the presence of significant tourist and socio-economic activity represented by religious tourism, and it occur due to various reasons such as urbanization. The purpose of this study is to apply a Markov model to analyze and predict the behavior of transforming the use of land in Karbala city over time. This can include the conversion of agricultural land, or other areas into residential, commercial, industrial land uses. The process of urbanization is typically driven by population growth, economic development, based on a set of probabilities and transitions bet

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