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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
Thu Jun 30 2016
Journal Name
Al-kindy College Medical Journal
Integrated Problem Based Learning (PBL) Evaluation by Students in Kerbala Medical College
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Background: Scientific education aims to be inclusive and to improve students learning achievements, through appropriate teaching and learning. Problem Based Learning (PBL) system, a student centered method, started in the second half of the previous century and is expanding progressively, organizes learning around problems and students learn about a subject through the experience of solving these problems.Objectives:To assess the opinions of undergraduate medical students regarding learning outcomes of PBL in small group teaching and to explore their views about the role of tutors and methods of evaluation. Type of the study: A cross-sectional study.Methods: This study was conducted in Kerbala Medical Colleges among second year students

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Publication Date
Tue Mar 20 2018
Journal Name
Mustansiria Dental Journal
A comparative Study in the Antibacterial effect of Eugenol as Hand Wash Material with two Types of Soap
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Hands have consistently been an important vehicle in the transmission of disease (1). Thus, thorough hand-washing remains the single most important factor in preventing infection specially in hospitals and labs.Twenty-nine non-clinical volunteers (do not work or come in contact with a clinical or hospital setting) that lacked visible skin injuries, eczema or apparent skin disease were used, those subjects were all tested by a material of each of the three used in the study weekly and laboratory tests were done pre- and post washing.All three material were effective , Eugenol extract as effective as the bar and lotion soap. And this was confirmed statistically.Eugenol has a great antibacterial action even in small concentration and t

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Publication Date
Tue Dec 01 2020
Journal Name
Journal Of Economics And Administrative Sciences
Fuzzy Analytic Hierarchy Process FEAHP to Prioritize The Evaluation of The Main and Subsidiary Criteria in B2B Industrial Market Sectors – Applied Research
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The research aims to define the main and subsidiary criteria for evaluating the industrial market sectors and proposing a model for arranging these criteria according to priority and knowing the highest criteria in terms of relative importance in the General Company for Automobile Trade and Machinery, and for the purpose of establishing this model, experiences in the concerned company were approved, and this study proposes a multi-criteria decision model According to the FEAHP, the expanded fuzzy hierarchical analysis method enables the commercial company to develop clear strategic policies on which the company’s management system depends on determining criteria for evaluating and selecting market sectors and making appropriate

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Publication Date
Sun Dec 15 2019
Journal Name
Journal Of Baghdad College Of Dentistry
Evaluation of Crestal Bone Resorption around Dental Implants in Flapped and Flapless Surgical Techniques Depending on Cone Beam CT Scan (Comparative Study)
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Background: The long term survival of dental implants is evaluated by the amount of crestal bone loss around the implants. Some initial loss of bone around dental implants is generally expected. There is reason to believe that reflecting a mucoperiosteal flap promotes crestal bone loss in the initial phase after an implant has been inserted. The surgical placement of a dental implant fixture is constantly changing and in recent years, there has been some interest in developing techniques that minimize the invasive nature of the procedure, with flapless implant surgery being advocated. The purpose of this study was to compare the radiographic level of the peri- implant bone after implant placement between traditional flapped surgery and f

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Publication Date
Tue Feb 25 2020
Journal Name
Open Access Macedonian Journal Of Medical Sciences
Evaluation of Hepatocyte Growth Factor in Iraqi Patients with Acute Myeloid Leukemia: Its Correlation with Clinical Parameters and Response to Induction Therapy
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BACKGROUND: Hepatocyte growth factor (HGF) is a proangiogenic factor that exerts different effects over stem cell survival growth, apoptosis, and adhesion. Its impact on leukemogenesis has been established by many studies. AIM: This study aimed to determine the effect of plasma HGF activity on acute myeloid leukemia (AML) patients at presentation and after remission. PATIENTS AND METHODS: This was a cross-sectional prospective study of 30 newly-diagnosed, adult, and AML patients. All patients received the 7+3 treatment protocol. Patients’ clinical data were taken at presentation, and patients were followed up for 6 months to evaluate the clinical status. Plasma HGF levels were estimated by ELISA based methods in the pa

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Publication Date
Wed Dec 30 2020
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Evaluation of the Effect of Topical Artemisia dracunculus Administration on Serum Levels of Selected Interleukins and Spleen Index in Imiquimod-Induced Psoriasis in Male Mice Compared to Clobetasol Propionate (Dermovate (R)) Ointment
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Psoriasis is a long-lasting autoimmune disease that is characterized by swollen skin patches. Normally, these skin patches are dark, swollen, itchy and scaly. The single application of the innate TLR7/8 ligand Imiquimod (IMQ) in mice easily induces a dermatitis that closely resembles human psoriasis, critically dependent on the axis of IL-23/IL-17. Artemisia dracunculus prepared as an ointment and has been used topically to mice before imiquimod application. The results of the current study showed that A. dracunculus ointment can significantly reduce psoriasis area and severity index in (A. dracunculus ointment + imiquimod group as compared with both control group and (vehicle ointment + imiquimod) group.

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Publication Date
Mon Jan 01 2024
Journal Name
Journal Of Medicine And Life
Antimicrobial photodynamic therapy using a low-power 650 nm laser to inhibit oral Candida albicans activity: an in vitro study
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Publication Date
Wed May 29 2019
Journal Name
Iraqi Journal Of Physics
Effect of sulfuric acid solution on thermal conductivity and impact strength of epoxy resin reinforced by silicon dioxide powder
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In this search, Ep/SiO2 at (3, 6, 9, 12 %) composites is prepared by hand Lay-up method, to measure the change in the thermal conductivity and Impact Strength of epoxy resin before and after immersion in H2SO4 Solution with a 0.3N for 10 days. The results before immersion decreases with the increase of the weight ratios of the reinforcement material (SiO2), It changed from (82.6×10-2 to 38.7×10-2 W/m.°C) with change weight ratios from (3 to 12) % respectively, but after immersion time in the chemical solution where it was (65.6×10-2 W/m.°C) at the weight ratios (6 %) and became (46.6 × 10-2 W/m.°C) after immersion in sulfuric acid. The results of the Impact strength decreased by increasing the percentage weight ratio, it changed f

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Crossref
Publication Date
Thu Nov 03 2016
Journal Name
Int. J. Pharm. Sci. Rev. Res.
Impacts of simultaneous administration of omega-3 fatty acids with amoxicillin/clavulanic acid on albino rats' liver and bile
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Most drugs undergo some metabolism in the liver before excretion by the kidneys or bile. Thus, it is not surprising that liver injury may be provoked due to its exposure to various drugs and compounds. Drug-induced cholestatic liver injury may occur particularly under conditions of increased drug concentrations, genetic alterations in expression of enzymes or transporters. Additionally, the drug-induced cholestasis can be caused by direct toxic effects of drugs or their metabolites on different hepatic cell types or through an immune-mediated process. Amoxicillin/ clavulanic acid, an antibiotic that is therapeutically utilized for the treatment of a number of bacterial infections. Omega-3 fatty acids are unsaturated fatty acids that have ro

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Publication Date
Sat Jan 05 2019
Journal Name
Iraqi Journal Of Physics
Synthesis of Au –Ag– Cu trimetallic alloy nanoparticles prepared by electrical exploding wire technique in distilled water
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Formation of Au–Ag–Cu ternary alloy nanoparticles (NPs) is of particular interest because this trimetallic system have miscible (Au–Ag and Au–Cu) and immiscible (Ag– Cu) system. So there is a possibility of phase segregation in this ternary system. At this challenge it was present attempts synthetic technique to generate such trimetallic alloy nanoparticles by exploding wire technique. The importance of preparing nanoparticles alloys in distilled water and in this technique makes the possibility of obtaining nanoparticles free of any additional chemical substance and makes it possible to be used in the treatment of cancer or diseases resulting from bacterial or virus with least toxic. In this work, three metals alloys Au-Ag-Cu

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