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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 Jun 22 2022
Journal Name
Journal Of Oral &dental Research
The Antibacterial Effect of Tea Tree Oil, Clove Oil and 3% Sodium Hypochlorite against Enterococcus faecalis in Endodontics: An in vitro Study
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Irrigation has significant role in endodontic treatment, many types of antimicrobial irrigation solutions have been used, but due to the ineffectiveness, safety concerns and side effects of this irrigation, the herbal alternatives for endodontic irrigants might be beneficial. Objectives This study compared the in vitro effectiveness of tea tree oil and clove oil as possible irrigants in endodontics against Enterococcus faecalis in comparison with 3% Sodium hypochlorite. Materials and Methods E. faecalis was isolated from patients in need for endodontic treatment; VITEK was employed for E. faecalis isolate conformation. Muller Hinton agar was prepared with 100μl of freshly prepared suspension of E.faecalis. Wells of 6mm diameter and 4mm dep

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Publication Date
Wed Jun 22 2022
Journal Name
Journal Of Oral &dental Research
The Antibacterial Effect of Tea Tree Oil, Clove Oil and 3% Sodium Hypochlorite against Enterococcus faecalis in Endodontics: An in vitro Study
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Irrigation has significant role in endodontic treatment, many types of antimicrobial irrigation solutions have been used, but due to the ineffectiveness, safety concerns and side effects of this irrigation, the herbal alternatives for endodontic irrigants might be beneficial. Objectives This study compared the in vitro effectiveness of tea tree oil and clove oil as possible irrigants in endodontics against Enterococcus faecalis in comparison with 3% Sodium hypochlorite. Materials and Methods E. faecalis was isolated from patients in need for endodontic treatment; VITEK was employed for E. faecalis isolate conformation. Muller Hinton agar was prepared with 100μl of freshly prepared suspension of E.faecalis. Wells of 6mm diameter and 4mm dep

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Publication Date
Thu Feb 01 2024
Journal Name
Journal Of Engineering
Rutting Prediction of Asphalt Mixtures Containing Treated and Untreated Recycled Concrete Aggregate
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Rutting is a crucial element of the mechanical performance characteristics of asphalt mixtures, which was the primary target of this study. The task involved substituting various portions of virgin coarse aggregate with recycled concrete aggregate materials that had been treated or left untreated at rates ranging from 25 to 100%, with a constant increase of 25%. The treatment process of recycled concrete aggregate involved soaking in acetic acid, followed by a mechanical process for a short time inside a Los Angeles machine without the balls. This research utilized two primary tests: the standard Marshall test to identify the optimal asphalt contents and the volumetric characteristics of asphalt mixtures. The other one w

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Publication Date
Wed May 17 2023
Journal Name
International Journal Of Computational Intelligence Systems
Prediction of ROP Zones Using Deep Learning Algorithms and Voting Classifier Technique
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Abstract<p>Retinopathy of prematurity (ROP) can cause blindness in premature neonates. It is diagnosed when new blood vessels form abnormally in the retina. However, people at high risk of ROP might benefit significantly from early detection and treatment. Therefore, early diagnosis of ROP is vital in averting visual impairment. However, due to a lack of medical experience in detecting this condition, many people refuse treatment; this is especially troublesome given the rising cases of ROP. To deal with this problem, we trained three transfer learning models (VGG-19, ResNet-50, and EfficientNetB5) and a convolutional neural network (CNN) to identify the zones of ROP in preterm newborns. The dataset to train th</p> ... Show More
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Publication Date
Sat Jun 19 2021
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
The Pharmacological Effects of Kappa Carrageenan on Different Human Cell Lines and Genomic DNA: An in vitro study
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Carrageenan extract is a compound of sulfated polyglycan that is taken out from red seaweeds. Being hydrocolloid in nature, carrageenan has gelling, emulsifying and thickening properties allowing it to be commonly used in the oral healthcare products and cosmetics. Due to its bioactive compounds, carrageenan has been shown to have antimicrobial, antiviral, and antitumor properties. The purpose of this work is to study the probable use of carrageenan on the diseases that are related to oral cavity and on the genomic DNA in in vitro experimental model

In this study, the effects of k-carrageenan on four different cell lines related to the cancer and normal cells which cultured on selective media were done. Moreover, the eff

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Publication Date
Wed Nov 28 2018
Journal Name
International Journal Of Engineering &amp; Technology
Using Polyurethane Coating of Concrete Pipes with Acid Attack Resistance in Sewer Lines
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One of the most important challenges facing the designers of the sewerage system is the corrosion of sewers due to the influence of sewerage contaminates which lead to failure of the main lines of sewers. In this study, a reference mix of 1: 1.5: 3 was used and the 4% Flocrete PC200 by weight of cement was added to the same mixing ratio in the second mixture. Twenty-four samples were tested for each mixture, 12 of which were used to compression strength test in ages (7, 14 and 28) day and six samples were submerged after 28 days of wet treatment at (5 and 10) % concentrations of sulfuric acid. The other six samples were painted after 28 days of wet treatment with coating Polyurethane and after 24 hours were flooded with a concentrat

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Publication Date
Fri Sep 25 2020
Journal Name
International Journal Of Drug Delivery Technology
Simultaneous Determination of Trace Mefenamic Acid in Pharmaceutical Samples via Flow Injection Fluorometry
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Mefenamic acid belongs to non-steroidal anti-inflammatory drugs that are used widely for the treatment of analgesia. Our aim from this study is to establish a new assay for the quantitative determination of mefenamic acid (MFA) in the pharmaceutical sample by two sensitive and rapid flow injection-fluorometric methods. A homemade fluorometer was used in fluorescence measurements, which using solid-state laser diode 405 and 532 nm as a source, combined with a continuous flow injection technique. The first method depends on the effect of MFA on calcein blue (CLB) fluorescence at 405 nm. Another method is a study of rhodamine-6G (Rh-6G) fluorescence after adding MFA, and recording at 532 nm. Optimum parameters as fluorescent dye concen

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Publication Date
Fri Jun 16 2023
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
The Possible Protective Effect of Cinnamic Acid on Ovalbumin-Induced Asthma in Mice
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Asthma is a chronic respiratory disorder in which immunological and structural cells play a role. The limits of conventional medicines necessitate the development of innovative therapeutic techniques for asthma. In the present study, we investigated the possible protective effect of cinnamic acid (CA) on ovalbumin-induced asthma in a mouse model. Sixty albino male mice BALB/c type weighing (20-30) grams were chosen at random and divided into five groups each one contains 12 animal: Group I: PBS/liquid paraffin control. Group II: asthma model group. Group III: cinnamic acid control group; mice received cinnamic acid (50 mg/kg) in liquid paraffin orally by gavage. Group IV: asthma model / group of (25 mg / kg) cinnamic acid; mice received

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Publication Date
Sun Jun 01 2014
Journal Name
Baghdad Science Journal
Preparation and Identification of some new Pyrazolopyrin derivatives and their Polymerizations study
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Preparation and Identification of some new Pyrazolopyrin derivatives and their Polymerizations study

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Publication Date
Wed Jun 01 2022
Journal Name
International Journal Of Early Childhood Special Education (int-jecs)
Building a comprehensive quality scale school sports activities from the standpoint of physical education teachers in the directorates of education in the Governorate of Baghdad
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The purpose of this paper is to building a comprehensive quality scale for school sports activities from the standpoint of physical education teachers in the directorates of education in the Governorate of Baghdad. The researchers used the descriptive approach with the survey method because it is the most appropriate to the nature of the problem and to achieve the objectives of the research .The good selection of the sample will reduce sampling errors, which enhances the honesty and accuracy of the data, which is representative of the research community and is always linked to its representation of the community and the possibility of generalizing its results to the group from which it was taken, as it represents the research community with

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