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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
Sat Feb 28 2026
Journal Name
Journal Of Baghdad College Of Dentistry
Effect of orthodontic tooth movement on salivary levels of Interleukin-1beta, Tumor Necrosis Factor-alpha, and C- reactive protein
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Background: Orthodontic force is considered to stimulate cells in the periodontium to release many mediators such as cytokines which play a responsible role for periodontal and alveolar bone remodeling, bone resorption and new bone deposition. Aim of this study was carried out to estimate changes of the (interleukin-one beta, tumor necrosis factor – alpha and C-reactive protein) levels in unstimulated whole saliva during the leveling stage of orthodontic tooth movement. Materials and methods: The sample consisted of thirty adult patients (12 males and 18 females) with ages ranges (19-23) years. Each sample had Class I and Class II malocclusion dental classification and required bilateral extraction of their maxillary first premolars, und

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Publication Date
Sun Jun 30 2024
Journal Name
Iraqi Geological Journal
Electrical Resistivity Synthetic Modeling and Field Survey for Subsurface Features Investigation of the Borsippa Archaeological Site, Babylon Governorate, Middle Iraq
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The selection of proper field survey parameters of electrical resistivity can significantly provide efficient results within a reasonable time and cost. Four electrode arrays of 2D Electric Resistivity Imaging (ERI) surveys were applied to characterize and detect subsurface archaeological bodies and to determine the appropriate array type that should be applied in the field survey. This research is to identify the subsurface features of the Borsippa archaeological site, Babylon Governorate, Middle Iraq. Synthetic modeling studies were conducted to determine the proper array and parameters for imaging the shallow subsurface features or targets. The efficiency of many array types has been tested for the detection the buried archaeolog

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Publication Date
Sun Mar 01 2020
Journal Name
Al-mustansiriyah Journal Of Science
Evaluation the activity of Petroselinum crispum aqueous extract as promoter rooting for stem cuttings of some plants
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This study was conducted in the botanical garden, Department of biology, College of Science/ Mustansiriyah University in from (15 February to 15 March, 2019) under the natural environmental conditions in the greenhouse in order to evaluate the effectiveness of parsley aqueous extract as a promoter for rooting. The study included the use of aqueous extract of a plant Parsley (Petroselinum crispum) extract was used in concentrations (1.25, 2.5 g / l), compare with IBA in concentration (100 mg / L) with dipping time 24 hour for all treatments. The cutting stems were included Rosmarinus officinalis, Nerium oleander, Olea europaea, Plumeria alba, Hibiscus rosa, Pelargonium graveolens, and Myrtus communis. The following measurements were

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Publication Date
Thu May 31 2012
Journal Name
Al-khwarizmi Engineering Journal
Channel Estimation and Prediction Based Adaptive Wireless Communication Systems
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Wireless channels are typically much more noisy than wired links and subjected to fading due to multipath  propagation which result in ISI and hence high error rate. Adaptive modulation is a powerful technique to improve the tradeoff between spectral efficiency and Bit Error Rate (BER). In order to adjust the transmission rate, channel state information (CSI) is required at the transmitter side.

In this paper the performance enhancement of using linear prediction along with channel estimation to track the channel variations and adaptive modulation were examined. The simulation results shows that the channel estimation is sufficient for low Doppler frequency shifts (<30 Hz), while channel prediction is much more suited at

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Publication Date
Tue Mar 21 2023
Journal Name
Biomedical And Pharmacology Journal
Development and Validation of HPLC Method For the Detection of Fusidic Acid Loaded in Non-ionic and Cationic Nanoemulsion-Based Gels
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Fusidic acid (FA) is a well-known pharmaceutical antibiotic used to treat dermal infections. This experiment aimed for developing a standardized HPLC protocol to determine the accurate concentration of fusidic acid in both non-ionic and cationic nano-emulsion based gels. For this purpose, a simple, precise, accurate approach was developed. A column with reversed-phase C18 (250 mm x 4.6 mm ID x 5 m) was utilized for the separation process. The main constituents of the HPLC mobile phase were composed of water: acetonitrile (1: 4); adjusted at pH 3.3. The flow rate was 1.0 mL/minute. The optimized wavelength was selected at 235 nm. This approach achieved strong linearity for alcoholic solutions of FA when loaded at a serial concentrati

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Publication Date
Wed Mar 01 2023
Journal Name
International Journal Of Research In Social Sciences And Humanities
The Role of Value Chain Analysis as well as Programs and Performance Budget in Reducing Waste of Public Money(Applied Study)
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Programs and performance budget represents a sophisticated method of public budget numbers, which includes all allocations to be determined for each job or activity within a government entity, which is analyzed according to their needs and costs, and this method can be applied using one of the cost accounting techniques, which is the technique of analyzing the value chain that reduces costs by avoiding activities that do not add value and enhance activities that add value to the economic entity, the current research aims to develop the budget system in government entity by using the budget of programs and performance as a tool for planning and monitoring events and activities, thereby reducing the waste of public money by reducing unnecessa

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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
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 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
Mon Apr 01 2019
Journal Name
Plant Archive
EFFECT OF SOME GROWTH REGULATORS ON THE MULTIPLICATION AND STIMULATING THE PRODUCTION OF THE VOLATILE OIL OF ROSEMARY OFFICINALIS IN VITRO
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The experiment was conducted at the plant tissue culture laboratory of the Department of Horticulture and Garden Engineering College of Agricultural Engineering Sciences, University of Baghdad, in order to study the effect of some growth regulators on propagation an stimulation production of volatile oil compounds of rosemary plant Rosmarinus officinlis using two vegetative parts (apical and lateral buds). Factorial experiment was implemented in completely randomized design with twenty replications. The results indicated that culturing the apical meristem on the medium Murashige and Skoog (MS) media with 0.5 mg.l-1 (BA) with 0.1 mg.l-1 of NAA gave the highest response rate of 100%. As for the doubling stage, the levels of BAA and IAA (Indol

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