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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 14 2016
Journal Name
Journal Of Baghdad College Of Dentistry
Assessment of Enamel Surface after Debonding of Different Types of Esthetic Brackets (An In Vitro Study)
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Background: Debonding orthodontic brackets and removal of residual bonding material from the enamel surface include critical steps that may cause enamel damage. The aim of the present study was to evaluate and compare the site of bond failure and enamel surface damage after debonding of three types of esthetic brackets (composite, ceramic, sapphire) bonded with light cure composite and resin-modified glass ionomer adhesive. Materials and methods: Seventy two maxillary premolars teeth were divided into three groups each group consisted of 24 teeth according to the type of brackets. Each group was subdivided into two subgroups (12 teeth for each) according to the bonding material that was used. After 7 days of bonding procedure, the brackets

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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)
The Relationship between Uric Acid Concentration and Some of Plasma Lipids in Patients with C. V. Disease in General Hospital of Al-Nasseriya
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         Cardiovascular disorders  are  refer to the class of diseases that involve the heart or blood vessels (arteries and veins). While the term technically refers to any disease that affects the cardiovascular system. Cholesterol is classified as a sterol (a contraction of steroid and

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Publication Date
Sun Oct 01 2023
Journal Name
Bulletin Of Electrical Engineering And Informatics
A novel data offloading scheme for QoS optimization in 5G based internet of medical things
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The internet of medical things (IoMT), which is expected the lead to the biggest technology in worldwide distribution. Using 5th generation (5G) transmission, market possibilities and hazards related to IoMT are improved and detected. This framework describes a strategy for proactively addressing worries and offering a forum to promote development, alter attitudes and maintain people's confidence in the broader healthcare system without compromising security. It is combined with a data offloading system to speed up the transmission of medical data and improved the quality of service (QoS). As a result of this development, we suggested the enriched energy efficient fuzzy (EEEF) data offloading technique to enhance the delivery of dat

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Publication Date
Sat Jun 01 2024
Journal Name
Iaes International Journal Of Artificial Intelligence (ij-ai)
A novel fusion-based approach for the classification of packets in wireless body area networks
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This abstract focuses on the significance of wireless body area networks (WBANs) as a cutting-edge and self-governing technology, which has garnered substantial attention from researchers. The central challenge faced by WBANs revolves around upholding quality of service (QoS) within rapidly evolving sectors like healthcare. The intricate task of managing diverse traffic types with limited resources further compounds this challenge. Particularly in medical WBANs, the prioritization of vital data is crucial to ensure prompt delivery of critical information. Given the stringent requirements of these systems, any data loss or delays are untenable, necessitating the implementation of intelligent algorithms. These algorithms play a pivota

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Publication Date
Sun Oct 01 2023
Journal Name
Bulletin Of Electrical Engineering And Informatics
A novel data offloading scheme for QoS optimization in 5G based internet of medical things
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The internet of medical things (IoMT), which is expected the lead to the biggest technology in worldwide distribution. Using 5th generation (5G) transmission, market possibilities and hazards related to IoMT are improved and detected. This framework describes a strategy for proactively addressing worries and offering a forum to promote development, alter attitudes and maintain people's confidence in the broader healthcare system without compromising security. It is combined with a data offloading system to speed up the transmission of medical data and improved the quality of service (QoS). As a result of this development, we suggested the enriched energy efficient fuzzy (EEEF) data offloading technique to enhance the delivery of dat

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Publication Date
Sun Jun 03 2012
Journal Name
Baghdad Science Journal
Study the effect of the mixture aquatic extract of Peganum harmala seeds and Pericarp of Punica granutum on viability of protoscolices of Echinococcus granulosus in vitro and in vivo
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This study included the preparation of the mixture aquatic extracts of Peganum harmala seeds and Pericarp of Punica granutum at concentration (10+50) ?(15+55)? (20+60) mgml .To study the influence of the mixture on the percentage of vitality of the protoscolices of E. granulosus In vitro, as the vitality of protoscolices had caused complete death when the using concentration at time 120,90,60 minute respectively. Also study the effect of mixture in white mice with infectious protoscolices In vivo and study the change occurred in the averages of the weights of the liver and spleen and the averages of its distension In vivo in processed group with mixture at concentration (15+55) , (10+50)mgml ,as which was approach to the negative gro

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Publication Date
Sun Sep 15 2019
Journal Name
Biochemical And Cellular Archives
VARIOUS APPLICATIONS OF CARBAZONE DERIVATIVES AND THEIR METAL COMPLEXES : A REVIEW
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Carbazone Derivatives (CD) (semicarbazone, semithiocarbasone) are produced by the condensation reaction between a aldehyde (or ketone) with a carbazide derivatives (semicarbazide, semithiocarbazide). CD and their metal complexes existent a wide range of implementation that stretch from their ply in the medicinal and pharmaceutical area because of their major significant pharmacological characteristic such as anti-fungal,anti-bacterial, anti-cancer, anti-human immunodeficiency virus, anti-inflammation, anti-neoplastic,inhibition corrosion, antioxidation, antiradical. This paper reviews the definition, importance and various applications of carbazone derivatives with transitional meta

Publication Date
Sat Jan 01 2022
Journal Name
Journal Of University Of Anbar For Pure Science
A Short Review: Chemistry of Curcumin and Its Metal Complex Derivatives
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This review covers recent progress in the synthesis of curcumin and the bioactivity of semisynthetic and synthetic analogs of curcumin. The review also shows how curcumin is a useful intermediate for the synthesis of more complex organic molecules; historical perspective; the process of preparing the metal complexes and characterization the produced complexes using various spectral and other techniques; shows the importance of curcumin and its derivatives for their potential applications in medical devices and broad-spectrum of medical application such as antibiotic ointment, alternative therapeutics, antifungal, and antibacterial activities

Publication Date
Sun Jun 05 2016
Journal Name
Baghdad Science Journal
Sizing and Thermal Stability of Prepared Tetraaminophthalocyaninatocopper(II) Derivatives-grafted Polymers
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Different polymers were prepared by condensation polymerization of sebacic anhydride and adipic anhydride with ethylene glycol and poly(ethylene glycol). Their number average molecular weights were determined by end group analysis. Then, they were grafted on the prepared phthalocyaninatocopper(II) compounds with the general formula (NH2)4PcCu(II) having amino groups of 3,3',3'',3'''- or 4,4',4'',4'''- positions. All prepared polymers, compounds, and phthalocyaninatocopper(II)-grafted polymers were characterized by FTIR. The sizing measurements were carried out in 3,3',3'',3'''- (NH2)4PcCu(II) and 4,4',4'',4'''- (NH2)4PcCu(II) compounds with and without grafting polymers. The results showed that the grafting process led to decreasing in par

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Publication Date
Thu Dec 13 2018
Journal Name
Iraqi National Journal Of Nursing Specialties
Evaluation of Adolescents' Quality of life in Hilla City
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Objective(s): The present study describes the quality of life (QOL) among adolescents with age of (12-22) year old and identifies factors that may be associated with it. Methodology: A cross-sectional design is carried throughout to evaluate adolescents' quality of life in Hilla City for the period of September 2nd 2016 to November 6th 2016. The present study is conducted in different settings that include schools and colleges in Hilla City. A non-probability "purposive" sample of (144) participant is selected and comprised of (50%) males and (50%) females. An instrument is constructed for the intent of the st

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