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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 Sep 05 2010
Journal Name
Baghdad Science Journal
Effect of vibrio cholerae enterotoxin on phagocytosis in vitro
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Enterotoxin of Vibrio cholerae was extracted by cooling centrifuge at 6.000 rpm for 30 minntes. and filtrated by using milipore filter (0.22 ?m). The effect of crude enterotoxin on phagocytosis was studied by measuring the phagocytic index for 20 blood sample which were collected from healthy people and treated with enterotoxin in addition to control samples. From the results we found that phagocytic index of blood sample which were treated with enterotoxin was 42.9% while the phagocytic index of control blood samples was 64%. This means that there is a negative effect for the enterotoxin resulted from vibrio choleaa on the activity of phagocytic index.

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Publication Date
Tue Jan 01 2019
Journal Name
Journal Of Biotechnology Research Center
Leishmanicidal activity of Artemisinin against cutaneous Leishmaniasis, in Vitro
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Background: Cutaneous leishmaniasis (CL) is a neglected disease in tropical countries, including Iraq. Several studies have sought to examine chemotherapies for leishmaniasis treatment but most of them are of toxic and/or undesirable side effect, therefore, the need for investigating new fewer toxic therapies is essential. Aim of study: In this study, the cytotoxic effect of Artemisinin (ART), a novel herbal compound, was screened against the two forms, promastigotes and amastigotes, of the Iraqi isolate of Leishmania tropica, the causative agent of Baghdad boil. Material and methods: Different concentrations (1000, 500, 250, 125, 62.5, 31.25, 15.6 and 7.8) µM of Artemisinin were screened to investigate the leishmanicidal activity of th

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Publication Date
Wed Nov 15 2017
Journal Name
Journal Of Pharmacy And Biological Sciences
In-vitro effect of Artemisinin on L. tropica promastigotes
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Leishmaniasis is a widespread parasitic disease caused by Leishmania parasite, this disease considers a major health problem among worldwide. Treatments available are expensive or with cytotoxic side effect. This study was aimed to investigate the effect of an herbal new compound, called artemisinin, derived from a Chinese plant called Artemisia annua. Various concentrations were studied in vitro against L. tropica amastigotes by chamber counting to investigate its effect on the proliferation of promastigotes. Three incubation periods were adopted (24, 48, 72) hours. The results showed a significant decrease in surviving promastigotes, in parallel with the normal parasite count of untreated promastigotes, along the periods studied. Th

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Publication Date
Tue Sep 01 2020
Journal Name
Baghdad Science Journal
Modified Mathematical Model of Tumor Treatment by Radiotherapy
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In this research, a mathematical model of tumor treatment by radiotherapy is studied and a new modification for the model is proposed as well as introducing the check for the suggested modification. Also the stability of the modified model is analyzed in the last section.

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Publication Date
Sun Jun 30 2019
Journal Name
Journal Of The College Of Education For Women
(Evaluation and Mobility) As Two self-Organizing Posts for University Students
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One of the important goals in the learning process is to be effective learning through the self-direction of the learner , because it has an impact on the effort of learners , it is better to be a learner responsible for learning and independent of the acquisition of knowledge ,

اذ اكدتكثيرAs many have confirmed منFrom الدراساتStudies والادبياتAnd literature انthat فشلالكثير The failure of many منFrom الطلبةStudents فيin a تنظيمgroup المعلوماتthe information ومعالجتهاAnd processed اثناءduring عمليةProcess تعلمهمLearn them لاNo يرجعReturns الىto me انخفاضdrop فيin a درجةDegree ذكائهمTheir intelligence اوor عدمNo

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Publication Date
Thu Feb 13 2020
Journal Name
International Journal Of Environmental Research
Synthesis of a Novel Composite Sorbent Coated with Siderite Nanoparticles and its Application for Remediation of Water Contaminated with Congo Red Dye
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Abstract

Re-use of the byproduct wastes resulting from different municipal and industrial activities in the reclamation of contaminated water is real application for green projects and sustainability concepts. In this direction, the synthesis of composite sorbent from the mixing of waterworks and sewage sludge coated with new nanoparticles named “siderite” (WSSS) is the novelty of this study. These particles can be precipitated from the iron(II) nitrate using waterworks sludge as alkaline agent and source of carbonate. Characterization tests using X-ray diffraction (XRD), scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS) mapping revealed that the coating process was c

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Publication Date
Sat Dec 24 2022
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Study the Effect of 12-Hydroxyoctadecanoic Acid Concentration on Preparation and Characterization of Floating Organogels using Cinnarizin as Modeling Drug
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This work targeted studying organogel as a potential floating system. Organgel has an excellent viscoelastic properties, floating system posses a depot property.  Different formulations of 12-hydroxyoctadecanoic acid (HOA) in sesame oil were gelled and selecting F1, F3 and F5 HOA organogels for various examinations: tabletop rheology, optical microscopy, and oscillatory rheology studies. Also, the floating properties studies were conducted at in vitro and in-vivo levels. Lastly, the in-vitro release study using cinnarizine (CN) was to investigate the organogel depot property. Based on the results, the selected concentrations of HOA in sesame oil organogels showed temperature transitions fr

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Publication Date
Tue Oct 02 2018
Journal Name
Iraqi Journal Of Physics
Study of in vitro and in vivo free radical scavenging activity for radioprotection of cerium oxide nanoparticles
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Nanoceria have shown numerous unique characteristics, such as biocompatibility and are excellent agents for biological applications. The aim of this study is to investigate cerium oxide nanoparticles for 2, 2- diphenyl-1-picryl-hydrazyl-hydrate (DPPH) free radical scavenging activity and their ability to offer protection against ionizing radiation. In vitro antioxidant activity study of nanoceria particles has shown good free radical scavenging activity for DPPH radical assayed within a concentration range of 0.01 to 0.05 g/l, at higher concentrations of nanoparticles showed reverse trend in absorbance and inhibition indicating this finite rang of concentration is suitable for scavenging free radicals, also nanoparticles were found to ha

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Publication Date
Thu Feb 01 2024
Journal Name
Indonesian Journal Of Chemistry
Synthesis, Characterization, and Evaluation of MCF-7 (Breast Cancer) for Schiff, Mannich Bases, and Their Complexes
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A new synthesis of Schiff (K) 6 and Mannich bases (Q) 7 had formed compound (Q) 7 by reacting compound (K) with N-methylaniline at the presence of formalin 35% to given Mannich base (Q). Additionally, new complexes were formed by reacting Schiff base (K) with metal salts CuCl2·2H2O, PdCl2·2H2O, and PtCl6·6H2O by 2:1 of M:L ratio. New ligands and their complexes were characterized, exanimated, and confirmed through several techniques, including FTIR, UV-visible, 1H-NMR, 13C-NMR spectroscopy, CHN analysis, FAA, TG, molar conductivity, and magnetic susceptibility. These compounds and their complexes were screened against breast cancer cells. It was determined that several of these compounds had a significant anti-breast cancer effec

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Publication Date
Tue Mar 30 2021
Journal Name
Baghdad Science Journal
Synthesis, Characterization and Biological Activity Evaluation of Some Pyrazoles, Thiazoles and Oxazoles Derived from 2-Mercaptoaniline
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    Synthesis of 2-mercaptobenzothiazole (A1) is performed from the reaction of  o-aminothiophenol and carbon disulfide CS2 in ethanol under basic condition. Compound (A1)  is reacted with chloro acetyl chloride to give compound (A2). Hydrazide acid compound (A3) is obtained from the reaction of compound (A2) with  hydrazine hydrate in ethanol under reflux in the presence of glacial acetic acid .The reaction of hydrazide acid compound (A3) with ethyl acetoacetate gives pyrazole compound (A4). The new hydrazone  compound (A5) was prepared from the reaction of compound (A3) with  benzaldehyde. Reaction of compound

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