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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 Mar 11 2014
Journal Name
Baghdad Science Journal
'I-V Characteristic and Crystal Structural Of a-As/c-Si Heterojunctions
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In this research the a-As flims have been prepared by thermal evaporation with thickness 250 nm and rata of deposition (1.04nm/sec) as function to annealing temperature (373 and 373K), from XRD analysis we can see that the degree of crystalline increase with , and I-V characteristic for dark and illumination shows that forward bias current varieties approximately exponentially with voltage bias. Also we found that the quality factor and saturation current dependence on annealing temperatures.

Publication Date
Mon Jan 09 2017
Journal Name
Nauchform
Creolized Text as a Means of Modern Communication: Verbal and Visual Components
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The article considers a creolized text as a means of modern communication, describing its key verbal and visual components; the relationship of concepts polycode and creolized text has been shown; the universal basic image features have been called; the following kinds of creolized texts have been distinguished; it has been proved that the effective means of attracting the attention of the addressee is the use of expressive font features, which are divided into two groups: topographics (mechanisms of varying of areal syntagmatic of a text) and supragraphcs (change of typeface of font).

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Publication Date
Tue Jan 08 2019
Journal Name
Iraqi Journal Of Physics
Preparation and characterization of mixed SnO2:CdO thin films as gas sensor
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In this study, tin oxide (SnO2) and mixed with cadmium oxide (CdO) with concentration ratio of (5, 10, 15, 20)% films were deposited by spray pyrolysis technique onto glass substrates at 300ºC temperature. The structure of the SnO2:CdO mixed films have polycrystalline structure with (110) and (101) preferential orientations. Atomic force microscopy (AFM) show the films are displayed granular structure. It was found that the grain size increases with increasing of mixed concentration ratio. The transmittance in visible and NIR region was estimated for SnO2:CdO mixed films. Direct optical band gap was estimated for SnO2 and SnO2 mixed CdO and show a decrease in the energy gap with increasing mixing ratio. From Hall measurement, it was fou

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Publication Date
Mon Oct 22 2018
Journal Name
Journal Of Economics And Administrative Sciences
The challenges facing the Insurance sector in Iraq Analytical study in Iraqi insurance companies (National insurance company as model)
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Most of World nations are striving to provide the necessary needs to protect their economic properties assets against natural or abnormal disasters that may be inflicted on such property and the means that used by such countries to reduce the damages is insurance, whereas insurance as a system that collects and distributes different risks into the group thus  to achieve a social symbiosis between individuals. The system works to transfer the risks from the individual to the group and then distributes the losses to all members of the group.

According to the importance of the insurance sector and the need to develop it as well as working on improving its performance, this search aims to identify the ac

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Publication Date
Sun Sep 27 2020
Journal Name
Journal Of The College Of Education For Women
Problems Facing Working Women in the Labor Market (The Mall) as a Model:a Field Study in Al-RusafaArea/ Baghdad
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Most studies and research have tried to shed light on unemployment and employment in general, with less focus on the problems facing working women and the resulting social and economic consequences that threaten their human and professional lives. For women, working is one of the basic necessities for the sustainability of human life, and it constitutes an essential axis for both sexes and through it. It also gives a person the status and social status where the individual finds a ready opportunity to practice his intentions and desires, test his abilities and talents, and achieve his ambitions. The availability of full employment in general and the joining of women to the labor market is an important and fundamental factor in the sustai

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Publication Date
Wed Jun 01 2022
Journal Name
Journal Of The College Of Languages (jcl)
The passive As a grammatical phenomenon in four selected textbooks: Das Passiv Als grammatisches Phӓnomen in vier ausgewӓhlten Lehrwerken
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The research work is "The passive voice as a grammatical phenomenon in four selected textbooks". The research deals with the grammatical phenomenon passive in German. The research consists of two parts, the theoretical and the empirical part. The present research work is divided into 3 sections:

The first section includes the definition of passive, passive types, process passive, state passive, passive with modal verbs, and other types of passive. The second section provides illustrations of the four selected textbooks. The third chapter presents the passive voice in textbooks, namely German language teaching for foreigners by Dora Schulz and Heinz Griesbach, Delfin von Aufderstrasse H. and others, Em von Balme, M. and others and

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Publication Date
Wed May 26 2021
Journal Name
Pharmaceuticals
Pt(II)-Thiocarbohydrazone Complex as Cytotoxic Agent and Apoptosis Inducer in Caov-3 and HT-29 Cells through the P53 and Caspase-8 Pathways
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In this study, a platinum(II) complex ([Pt(H2L)(PPh3)] complex) containing a thiocarbohydrazone as the ligand was tested as an anti-proliferative agent against ovarian adenocarcinoma (Caov-3) and human colorectal adenocarcinoma (HT-29) through MTT assays. Apoptotic markers were tested by the AO/PI double staining assay and DNA fragmentation test. Flow cytometry was conducted to measure cell cycle distribution, while the p53 and caspase-8 pathways were tested via immunofluorescence assay. Results demonstrated that the cytotoxic effect of the Pt(II)- thiocarbohydrazone complexes against Caov-3 and HT-29 cells was highly significant, and this effect triggered the activation of the p53 and caspase-8 pathways. Besides, apoptosis stimulated by th

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Publication Date
Sat Dec 21 2019
Journal Name
International Journal Of Pharmaceutical Quality Assurance
Evaluation of the Immunomodulatory Effects of Thymus vulgaris Ethanolic Leaf Extract Combination with Partially Purified Lipopolysaccharide from Proteus mirabilis in Mice
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The current study was carried out to study a high injection dose of the ethanolic extract thymus vulgaris leaf (500 ug /Kg) against the immune response combination with partially purified extracted Lipopolysaccharide ( LPS) from Proteus mirablis.Study groups were included four groups; Group I :treated with normal saline. Group II : treated with LPS antigen, Group III: injected subcutaneously ((500 ug /Kg) from ethanolic extract thymus vulgaris, group IV : injected subcutaneously (500 ug /Kg) from ethanolic extract thymus vulgaris leaf and LPS antigen, the immunological assays were measured through the phagocytic activity as (non specific immunity) after day 8 by using the phagocytic activity index.After day I4 the lymphocyte proliferations

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Publication Date
Thu Sep 13 2018
Journal Name
Baghdad Science Journal
Evaluation of Human Health Risks Associated with Exposure to Disinfection by-Products (Dbps) in Drinking Water of Wassit Province Southeast Iraq
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The toxicological risks and lifetime cancer risks associated with exposure to disinfection by-products (DBPs) including Halloacetic acids (HAAs) and trihalomethanes (THMs) compounds by drinking water in several districts in Wassit Province were estimated. The seasonal variation of HAAs and THMs compounds in drinking water have indicated that the mean values for total HAAs (THAAs) and total THMs (TTHMs) ranged from 43.2 to 72.4 mg/l and from 40 to 115.5 mg/l, respectively. The World health organization index for additive toxicity approach was non-compliant with the WHO guideline value in summer and autumn seasons and this means that THMs concentration has adverse toxic health effects. The multi-pathway of lifetime hu

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Publication Date
Mon Dec 30 2024
Journal Name
Wasit Journal For Pure Sciences
A New Class of Higher Derivatives for Harmonic Univalent Functions Established using a Generalized Fractional Integral Operator
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A new class of higher derivatives  for harmonic univalent functions defined by a generalized fractional integral operator inside an open unit disk E is the aim of this paper.

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