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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
Sun Jun 09 2019
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Formulation and Evaluation of Silymarin Microcrystals by In- Situ Micronization Technique
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Silymarin (SM) is a plant extract obtained from Silybum marianum( milk thistle) . It is class II type drug according to  Biopharmaceutics Classification System with low bioavailability due to its low solubility.

Micro/nanonization during crystallization, surface modification and crystal structure modification may improve the dissolution rate of poorly water-soluble drugs.

The aim of this study was to increase the water solubility and dissolution rate of SM by in-situ micronization using solvent change either by stirring or ultrasonic method. Stabilizers like Gelatin, PVP-K30, HPMC15, Pulullan were used to stabilize the prepared ultrafine crystals. Effect of type and concentration of hydrophilic polymer, solv

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Publication Date
Sun Dec 01 2019
Journal Name
Journal Of Economics And Administrative Sciences
Evaluation of waste sorting and recycling laboratory in Mahmudiya (case study)
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The daily practices of humans produce various types of waste, which are a threat to the health and environment surrounding it, especially after the increase in quantities as a result of population growth and technological development, and here came the need for recycling solid waste as one of the modern concepts that achieve environmental benefits, The aim of the research is to evaluate the project of sorting and recycling of solid waste in the district of Mahmoudiya and whether its work is sustainable ,Conforming to modern standards, using standard checklists to determine the gap between the current laboratory reality and the requirements of those standards , Using the case study methodology as the most appropriate approach

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Publication Date
Tue Dec 01 2020
Journal Name
International Journal Of Electrical And Computer Engineering
Analysis of threats and security issues evaluation in mobile P2P networks
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Technically, mobile P2P network system architecture can consider as a distributed architecture system (like a community), where the nodes or users can share all or some of their own software and hardware resources such as (applications store, processing time, storage, network bandwidth) with the other nodes (users) through Internet, and these resources can be accessible directly by the nodes in that system without the need of a central coordination node. The main structure of our proposed network architecture is that all the nodes are symmetric in their functions. In this work, the security issues of mobile P2P network system architecture such as (web threats, attacks and encryption) will be discussed deeply and then we prop

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Publication Date
Tue Jul 02 2024
Journal Name
Al-rafidain Journal Of Medical Sciences ( Issn 2789-3219 )
Formulation and Evaluation of Bilastine Thermosensitive Mucoadhesive Ophthalmic in situ Gel
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Background: Bilastine is a non-sedating, second-generation antihistamine used to treat urticaria and allergic conjunctivitis. Objective: to formulate and test bilastine as a mucoadhesive ophthalmic in situ gel in order to extend its presence at site for longer time and help treat conjunctivitis and allergic rhinitis. Methods: We prepared formulations using different concentrations of poloxamers (Poloxamer 407 (P407) and Poloxamer 188 (P188)) in combination with hydroxypropyl methyl cellulose (HPMC). The prepared formulas were evaluated for their physicochemical properties, sol-gel transition temperature, viscosity, mucoadhesive strength, drug release, and kinetic modeling. Results: The prepared in situ gels were clear and transparen

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Publication Date
Sat Jun 08 2024
Journal Name
Plant Science Today
Antibacterial and antioxidant activities of Alcea kurdica flower, leaf and root aqueous and organic extracts
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Global concerns are rising due to complications associated with the use of chemical agents and antibiotic resistance. Consequently, research focus has shifted towards the quest for effective agents of biological origin. The aim of the present study was to assess the antioxidant and antimicrobial potentials of aqueous and organic extracts derived from various parts of Alcea kurdica. Different parts of A. kurdica were obtained and prepared into leaf, flower and root powders. The powders were extracted with aqueous and organic solvents. The antimicrobial activity of these extracts was assessed against bacterial pathogens using the agar well-diffusion assay. Additionally, the antioxidant effects of the extracts were evaluated using the

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Publication Date
Sat May 01 2021
Journal Name
Journal Of Engineering
A Prediction Formula for The Estimation of Sediment Load in The Upper Reach of Al-Gharraf River
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The presence of deposition in the river decreases the river flow capability's efficiency due to the absence of maintenance along the river. In This research, a new formula to evaluate the sediment capacity in the upstream part of Al-Gharraf River will be developed. The current study reach lies in Wasit province with a distance equal to 58 km. The selected reach of the river was divided into thirteen stations. At each station, the suspended load and the bedload were collected from the river during a sampling period extended from February 2019 till July 2019. The samples were examined in the laboratory with a different set of sample tests. The formula was developed using data of ten stations, and the other three s

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Publication Date
Sun Sep 01 2013
Journal Name
Baghdad Science Journal
Synthesis ,spectroscopic study of Antipyryl azo 2-Naphthol and use it as new reagent for determination of Co(II) and Cu(II)
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A simple ,accurate and sensitive spectrophotometric method has been developed the determination of Cobalt(II) and Cupper (II) .The method is based on the chelation of Co(II) and Cu(II) ions with 4-(4´-pyrazolon azo) -2-Naphthol(APAN) in aqueous medium . The complexes have a maximum absorption at (513) and (506) nm and ? max 0.531×10 4 and 0.12×10 5 L.mol -1.cm -1 for Co(II) and Cu(II) respectively .The reagent and two complexes have been prepared in ethanolic solution.The stoichiometry of both complexes were found to be 1:2 (metal :legend) .The effects of various cations and anions on Co(II) and Cu(II) determination have been investigated .The stability constants and standard deviations for Co(II) and Cu(II) 0.291 x107 ,0.909X108 L.mol

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Publication Date
Wed Sep 14 2016
Journal Name
Journal Of Baghdad College Of Dentistry
Microleakage of Pit and Fissure Sealants after Using Different Occlusal Surface Preparation Techniques: An In Vitro Study
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Background: The marginal seal is essential for sealant success because penetration of bacteria under the sealant might allow caries onset or progression. The aim of the present study was to estimate and compare the microleakage of pit and fissure sealant after various methods of occlusal surface preparation. Materials and methods: Thirty non-carious premolars extracted for orthodontic reasons were equally divided into three groups. In group one, occlusal fissures were opened with round carbide bur, in group two, occlusal surfaces of the teeth were cleaned with a dry pointed bristle brush and samples of group three were cleaned with a slurry of fine flour of pumice in water using rubber cup. Then fissures of all teeth were etched using 35% p

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Publication Date
Sun Sep 06 2015
Journal Name
Baghdad Science Journal
The Bactericidal Effect of CO2 Laser on Pseudomonas aeruginosa Isolated from Wound and Burn Infections, In-Vitro
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A total of 60 cotton swabs are collected from patients suffering from burn wound and surgical site infections admitted to Baghdad Teaching Hospital and Burn Specialist Hospital in Baghdad city during 9/2013 to 11/2013. All cotton swabs are cultured initially on blood agar and MacConkey agar and subjected for standard bacteriological procedures for bacteriological diagnosis. Twenty samples out of sixty are identified as Pseudomonas aeruginosa by conventional methods. The results of antibiotic susceptibility test illustrate that the antibiotics resistance rate of Pseudomonas aeruginosa isolates is as follows:100% (2020) for ceftriaxone, cefepime and carbencillin, 70% (14/20) for amikacin, 65%(13/20) for tobramycin, ceftazidim and gentamycin,

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Publication Date
Tue Mar 01 2022
Journal Name
Journal Of Dentistry
In-vitro adhesive and interfacial analysis of a phosphorylated resin polyalkenoate cement bonded to dental hard tissues.
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Objectives: To assess the performance of a novel resin-modified glass-ionomer cement (pRMGIC) bonded to various tooth tissues after two-time intervals. Methods: 192 sound human molars were randomly assigned to 3 groups (n = 64): sound enamel, demineralised enamel, sound dentine. Sixty-four teeth with natural carious lesions including caries-affected dentine (CAD) were selected. All substrates were prepared, conditioned and restored with pRMGIC (30% ethylene glycol methacrylate phosphate (EGMP, experimental), Fuji II LC (control), Fuji IX, and Filtek™ Supreme with Scotchbond ™ Universal Adhesive. Shear bond strength (SBS) was determined after 24 h and three months storage in SBF at 37C. The debonded surfaces were examined using stereomi

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