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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
Tue Aug 30 2022
Journal Name
Research Journal Of Pharmacy And Technology
Correlation of Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers with serum GDF-15 in a group of hypertensive Iraqi patients
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The Growth Differentiation Factor -15 (GDF-15) is a member of the transforming growth factor β superfamily. İt represents an example of the stress response cytokines. It's mostly found in cardiac myocytes, adipocytes, macrophages, endothelial cells, and vascular endothelial cells, whether they're generated normally or not. GDF-15 levels have increased and are associated with cardiovascular risk. Aim of the study: To investigate the correlation between angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) with the level of plasma GDF-15 in a group of hypertensive patients. Materials and methods: A case-control study involved 90 individuals, 60 hypertensive patients (36 on ACE inhibitors and 24 on ARBs)

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Publication Date
Thu Jan 04 2018
Journal Name
Iraqi Journal Of Agricultural Sciences
Evaluation of Phyllanthus emblica extract as antibacterial and antibiofilm against biofilm formation bacteria.
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A study was conducted to evaluate the antibacterial effect of Phyllanthus emblica extract (ethanol:methanol, 1:1) against Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli at different concentrations, i.e. 0.625, 1.25, 2.50, 5.0, 10.0 and 20.0 mg/ml. The antibacterial activity was determined by the agar well diffusion method to investigate the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). The alcoholic extract of Phyllanthus emblica had the highest antibacterial activity at 20 mg/ml and 5 mg/ml except for Pseudomonas aeruginosa where the value of inhibition was between 20 and 10 mg/ml. The MIC concentrations were mostly very high and ranged from 5 to 1.25 mg/ml, while the MBC range fro

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Publication Date
Thu Jun 15 2017
Journal Name
Pakistan Journal Of Nutrition
Effect of Adding Dietary Conjugated Linoleic Acid to Broiler Diets on Production Performance and Fatty Acid Content in Meat
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Conjugated Linoleic Acid (CLA) is an essential polyunsaturated omega fatty acid that occurs naturally in vegetable oils. It also plays an important role in preserving meat for longer periods by preventing oxidation of other fats. Thus, it can be used in the production of functional foods with high biological value and low cholesterol levels by adding poultry diets. Objective: The aim of the present study was to evaluate the effect of adding CLA to broiler diets on production performance and fatty acid content in the meat. Methodology: One-day-old Ross-308 chicks were randomly distributed into four dietary treatment groups: control (0 g CLA kgG1 diet; A1), 0.5 g CLA kgG1 diet (A2), 0.75 g CLA kgG1 diet (A3) and 1 g CLA kgG1 diet (A4). Diets

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Publication Date
Wed Feb 22 2023
Journal Name
Iraqi Journal Of Science
Revealed of A novel Allele in Wasit – Iraqi Population
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The developments in forensic DNA technology have led us to perform this study in Iraqi population as reference database of autosomal Short Tandem Repeat (aSTR) DNA markers . A total of 120 unrelated individuals from Wasit province were analyzed at 15 STR DNA markers. Allele frequencies of DNA typing loci included in the AmpFlSTR1 IdentifilerTM PCR Amplification Kit panel from Applied Biosystems (D3S1358, vWA, FGA, D8S1179, D21S11, D18S51, D5S818, D13S317, D7S820, TH01, TPOX, CSF1PO, D19S433, D2S1338, D16S539) and several forensic efficiency statistical parameters were estimated from all the sample. the combined Matching Probability (CMP) using the 15 STR genetic loci in Iraqi population was estimated at 1 in 2.08286E-18 and the Combined

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Publication Date
Sun Dec 01 2019
Journal Name
Saudi Medical Journal
The diagnostic power of circulating micro ribonucleic acid 34a in combination with cancer antigen 15-3 as a potential biomarker of breast cancer
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Publication Date
Fri Nov 09 2018
Journal Name
Iraqi National Journal Of Nursing Specialties
Evaluation of Organization Structure as Component of Quality Improvement for Maternal and Child Health Promotion in Baghdad City’s Primary Health Care Centers
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A descriptive evaluation study is conducted on primary health care centers in Baghdad City in order to
evaluate the organization structure as component of quality improvement of maternal and child health promotion
from April 10th 2012 to May20th 2013. A total of (22) primary health care centers. Study instrument was
comprised of three questionnaires and overall items included in these questionnaire were (65) items. Data are
collected through the utilization of the developed questionnaire and the interview technique as means of data
collection. Data are analyzed through the application of descriptive statistical data analysis methods which
includes the measurement of the frequencies, percentages, and computation of mean

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Publication Date
Sun Sep 01 2013
Journal Name
Baghdad Science Journal
Six-coordinate oxime-imine cobalt(III) complexes with amino acid co-ligands; synthesis and characterisation
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In this publication, several six coordinate Co(III)-complexes are reported. The reaction of 2,3-butanedione monoxime with ethylenediamine or o-phenylenediamine in mole ratios of 2:1 gave the tetradentate imine-oxime ligands diaminoethane-N,N`-bis(2-butylidine-3-onedioxime) H2L1 and o-phenylenediamine-N,N`-bis(2-butylidine-3-onedioxime), respectively. The reaction of H2L1 and H2L2 with Co(NO3)2, and the amino acid co-ligands (glycine or serine) resulted in the formation of the required complexes. Upon complex formation, the ligands behave as a neutral tetradantate species, while the amino acid co-ligand acts as a monobasic species. The mode of bonding and overall geometry of the complexes were determined through physico-chemical and spectro

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Publication Date
Wed Mar 15 2023
Journal Name
Bionatura
Study the antioxidant of Matricaria chamomilla (Chamomile) powder: In vitro and vivo
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Oxidative stress is oxidative damage caused by free radicals and reactive oxygen species (ROS). These ROS can cause oxidative damage to cellular components, including membrane lipids, receptors, enzymes, proteins, and nucleic acids. It would eventually lead to cell apoptosis and the appearance of certain pathological conditions. This work investigates the antioxidant potentials of chamomile extract in vitro by evaluating the extract activity to scavenge 2,2-Diphenyl-1-picrylhydrazyl (DPPH), also in vivo by investigating its effects on oxidative stress-induced rats by assessing the total oxidant status (TOS) and total antioxidant capacity in the radiation exposed rats with and without the treatment with chamomile extract. The results

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Publication Date
Wed Mar 25 2020
Journal Name
International Journal Of Drug Delivery Technology
Preparation, Characterization and In-Vitro Diffusion Study of Different Topical Flurbiprofen Semisolids
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Flurbiprofen (FLB) is chemically 2-(3- fluoro-4-phenyl phenyl) propanoic acid. It is a nonsteroidal anti-inflammatory drug (NSAID) used in the treatment of rheumatoid arthritis and osteoarthritis. Oral administration of this drug is associated with severe gastrointestinal side effects like ulceration and gastrointestinal bleeding. The solution to this problem lies in the fact that topically applied NSAIDs are safer than orally. This study aims to prepare different topical semisolid formulation of FLB as cream base (o/w), (w/o) and gel base using different gel-forming agents in different concentrations. Comparing characterization properties in addition to release and diffusion study for all the prepared formulas to select the best on

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Publication Date
Thu Feb 07 2019
Journal Name
Iraqi Journal Of Laser
Evaluation of 532 nm Q-Switched Nd:YAG Laser and Acid Etching of Class V Composite Restoration: Comparative Histological Study
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Laser etching may be an alternative to acid etching of enamel and dentin. Several characteristics of irradiated dental hard tissues have been considered advantageous, microscopically rough surfaces without demineralization, open dentinal tubules without smear layer production and dentin surface sterilization. The aim of this study is to determine and compare histology the microleakage in class V cavity restored with a light cured composite after conditioning the samples(tooth surface) with 1-acid etching, 2-Q-switched Nd:YAG Laser etching and finally 3- acid and laser etching. Materials and methods: Twenty four non carious human extracted teeth were used in this study. The samples were equally grouped into four groups of six teeth each.

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