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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
Fri Jun 10 2022
Journal Name
V. International Scientific Congress Of Pure, Applied And Technological Sciences
Synthesis and characterisation of new Co(II), Zn(II) and Cd(II) complexes derived from oxadiazole ligand and 1,10-phenanthroline as co-ligand
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SYNTHESIS AND CHARACTERISATION OF NEWCo(II), Zn(II) AND Cd(II) COMPLEXES DERIVED FROM OXADIAZOLE LIGAND AND 1,10-PHENANTHROLINE AS Co-LIGAND

Publication Date
Thu Mar 03 2022
Journal Name
V. International Scientific Congress Of Pure, Applied And Technological Science (minar Congress)
synthesis and characterization of new Co(II), Zn(II) and Cd(II) complexes derived from oxadiazole ligand and 1,10-phenanthroline as co-ligand
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In this work, prepared new ligand namely 5-(2,4-dichloro-phenyl)-1,3,4-oxadiazole-2-(3H)-thion, was obtained from the 2,4-dichlorobenzoyl chloride with hydrazine, after that reaxtion with CS2/KOH in methanol.

Publication Date
Sun Sep 01 2013
Journal Name
Baghdad Science Journal
Spectroscopic Characterization and Antimicrobial Activities of Some Heavy Metals Complexes of 2-hydroxy phenyl piperonalidene
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An antibacterial and antifungal piperonal-derived compound and its Rh(III), Pd(II), Pt(IV), and Cd(II) metal complexes were synthesized and characterized by spectroscopic methods, conductivity, metal analyses and magnetic moment measurements. The nature of the complexes formed in ethanolic solution was studied following the molar ratio method. From the spectral studies, octahedral geometry was suggested for rhodium (III) and platinum (IV) complexes, while a square planer structure was suggested for palladium (II) complex and a tetrahedral geometry for cadmium (II) complex. Structural geometries of these compounds were also suggested in gas phase by using hyperchem-8 program for the molecular mechanics and semi-empirical calculations.

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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
Thu Dec 13 2018
Journal Name
Iraqi National Journal Of Nursing Specialties
Assessment of the Major Anti-Tuberculosis Drugs Available to Patients at Primary Health Care Centers in Baghdad City
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Objective: To assess the major anti-tuberculosis drugs available to patients at primary health care centers in Baghdad city. Methodology: A descriptive cross-sectional study design is carried out in order to achieve the objectives of the study by using the assessment technique in primary health care centers from December 29th, 2014 to July 10 th, 2015. probability sampling is select based on the study design. Eighteen primary health care centers are select according to criteria of sample to the study and for the purpose of the study, is select (6) sectors and (11) Primary Health Care Centers (PHCC) from Bagh

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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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Publication Date
Tue Jan 01 2019
Journal Name
Biochemical & Cellular Archives
Assessment of uric acid in patients of end-stage renal disease with hypertension and diabetic nephropathy and the risk of cardiovascular diseases
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The relationship of hyperuricemia to kidney disease, diabetes, hypertension and the risk of cardiovascular diseases remain controversial. The aim of this study is to evaluate the use of uric acid (UA) levels to find the higher risk of cardiovascular disease (CVD) in patients with end stage renal disease that have diabetic nephropathy (DN), nephropathy with hypertension (NH) and patients with both diabetic nephropathy with hypertension (DNH). This study deals with 115 patients with end-stage renal disease under hemodialysis sub-grouped into 35 patients with (DN), 40 patients with (NH), and 40 patients with (DNH). Some biochemical parameters were determined in the serum of all participants such as HbA1c, fasting blood glucose (FBG), UA, urea,

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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 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
Sun Jul 09 2023
Journal Name
Journal Of Engineering
Evaluation of Pedestrians Walking Speeds in Baghdad City
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This research examines the factors which influence pedestrian's walking speed in Baghdad. the variations in walking speed of pedestrians are related to pedestrian characteristics such as gender, age group, and clothing traditions. Using the established methodology, the counts of pedestrians were performed using manual and video counting. The case study was performed in two streets located in a highly crowded commercial zone at the city center of Baghdad: Al-Karada Dakhel and Al- Sina’a Street. Data were subjected to statistical analysis using IBM SPSS Statistics 19 software. It has been found that Iraqi pedestrians walk slower than other pedestrians in the developed countries or in the region with minimum walking speed of 29.85 m/min.

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