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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
Thu Sep 01 2011
Journal Name
Journal Of Economics And Administrative Sciences
Comparison of BASE methods with other methods for estimating the measurement parameter for WEBB distribution using simulations
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  Weibull distribution is considered as one of the most widely  distribution applied in real life, Its similar to normal distribution in the way of applications, it's also considered as one of the distributions that can applied in many fields such as industrial engineering to represent replaced and manufacturing time ,weather forecasting, and other scientific uses in reliability studies and survival function in medical and communication engineering fields.

   In this paper, The scale parameter has been estimated for weibull distribution using Bayesian method based on Jeffery prior information as a first method , then enhanced by improving Jeffery prior information and then used as a se

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Publication Date
Mon Nov 14 2022
Journal Name
Biomedicine
Cytotoxic effect of cloned EGFP gene on NCI-H727 cell line via genetically engineered gene transfer system
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Introduction and Aim: Cancers are a complex group of genetic illnesses that develop through multistep, mutagenic processes which can invade or spread throughout the body. Recent advances in cancer treatment involve oncolytic viruses to infect and destroy cancer cells. The Newcastle disease virus (NDV), an oncolytic virus has shown to have anti-cancer effects either directly by lysing cancer cells or indirectly by activating the immune system. The green fluorescent protein (GFP) has been widely used in studying the anti-tumor activity of oncolytic viruses. This study aimed to study the anticancer effect of a recombinant rNDV-GFP clone on NCI-H727 lung carcinoma cell line in vitro.   Materials and Methods: The GFP gene was inserted t

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Publication Date
Sat May 01 2021
Journal Name
Journal Of Physics: Conference Series
Operational assessment of biological wastewater treatment using advanced return-mass reactors based on principal component cluster analysis
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Abstract<p>In this study, field results data were conducted, implemented in 64 biofilm reactors to analyses extract organic matter nutrients from wastewater through a laboratory level nutrient removal process, biofilm layer moving process using anaerobic aerobic units. The kinetic layer biofilm reactors were continuously operating in Turbo 4BIO for BOD COD with nitrogen phosphorous. The Barakia plant is designed to serve 200,000 resident works on biological treatment through merge two process (activated sludge process, moving bed bio reactio MBBR) with an average wastewater flow of 50,000 m3/day the data were collected annually from 2017-2020. The water samples were analysis in the central labor</p> ... Show More
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Publication Date
Mon Jan 01 2024
Journal Name
Journal Of Engineering
Improving the Direction of Arrival Estimation Using the Parasitic Subspace Generated by Active-Parasitic Antenna (APA) Arrays
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The improvement in Direction of Arrival (DOA) estimation when the received signals impinge on Active-Parasitic Antenna (APA) arrays will be studied in this work. An APA array consists of several active antennas; others are parasitic antennas. The responses to the received signals are measured at the loaded terminals of the active element. The terminals of the parasitic element are shorted. The effect of the received signals on the parasites, i.e., the induced short-circuit current, is mutually coupled to the active elements. Eigen decomposition of the covariance matrix of the measurements of the APA array generates a third subspace in addition to the traditional signal and noise subspaces generated by the all-active ante

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Publication Date
Wed Jan 01 2014
Journal Name
Aes-atema International Conference Series - Advances And Trends In Engineering Materials And Their Applications,
Back filler friction spot welding of pure commercial copper sheets to AA1050 aluminum alloy sheets (experimental study)
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Publication Date
Wed Jan 10 2024
Journal Name
Journal Of Optics
Pulsed laser deposition of Pd/WO3 nanoparticles on Si nanostructure for highly sensitive room-temperature gas sensors
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Publication Date
Thu Mar 30 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Cytotoxic Assay of Nigella sativa Leaf Callus Extract (Thymol) on Hep-2 Cell Line Using ELISA Assay
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Extract from cell culture of medicinal plant like Nigella sativa have been assessed for its cytotoxic properties. Thymol is likely responsible for the theraputic effects of  Nigella sativa leaf callus extract. In this short study the inhibitory effect of Nigella sativa leaf callus extract (Thymol) has been studied on Human Lorgnx Epidrmoid Carcinoma (Hep-2) cell line during different exposure period of time (24, 48 and 72 hrs.) using different concentration of the extract (1000, 500, 400, 300, 200 and 100 µg/ml). The optical density of the Hep-2 cells has been readed on 492 nm wave length. Thymol –induced cytotoxicity was (500 µg/ml) which inhibit cell growing compared to the control and this

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Publication Date
Wed Jan 01 2020
Journal Name
Says Rev Pharm
Healing of apical periodontitis after minimally invasive endodontics therapy using Er,Cr:YSGG laser: A prospective clinical study
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Publication Date
Mon Mar 15 2021
Journal Name
Journal Of Baghdad College Of Dentistry
Comparison between the mesiodistal crown dimensions of second primary molar with stainless steel crowns from different companies
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Background: Due to the variations in tooth anatomy and size among different populations, this study aimed to compare the mesiodistal width of primary second molars in Iraqi children with the mesiodistal width of stainless-steel crowns from different companies. Materials and Methods: This cross-sectional study was conducted on 220 intact maxillary and mandibular primary second molars selected from boys and girls’ Iraqi children aged 8-9 years collected from different primary schools in Baghdad city. The mesiodistal dimensions of the selected teeth and the available maxillary and mandibular stainless-steel crowns from three different companies were measured by using a 3-D scanner, and then the whole measurements were calculated usin

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Publication Date
Wed Nov 01 2023
Journal Name
Case Studies In Thermal Engineering
Augmenting the thermal response of helical coil latent-heat storage systems with a central return tube configuration
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Low-temperature stratification, high-volumetric storage capacity, and less-complicated material processing make phase-changing materials (PCMs) very suitable candidates for solar energy storage applications. However, their poor heat diffusivities and suboptimal containment designs severely limit their decent storage capabilities. In these systems, the arrangement of tubes conveying the heat transport fluid (HTF) plays a crucial role in heat communication between the PCM and HTF during phase transition. This study investigates a helical coil tube-and-shell thermal storage system integrated with a novel central return tube to enhance heat transfer effectiveness. Three-dimensional computational fluid dynamics simulations compare the proposed d

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