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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
Wed Dec 27 2017
Journal Name
Al-khwarizmi Engineering Journal
Kinetic and Mechanism of Oxidation of Oxalic Acid by Cerium (IV)
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Kinetic and mechanism studies of the oxidation of oxalic acid by Cerium sulphate have been carried out in acid medium sulphuric acid. The uv- vis. Spectrophotometric technique was used to follow up the reaction and the selected wavelength to be followed was 320 nm. The kinetic study showed that the order of reaction is first order in Ce(IV) and fractional in oxalic acid. The effect of using different concentration of sulphuric acid on the rate of the reaction has been studied a and it was found that the rate decreased with increasing the acid concentration. Classical organic tests was used to identify the product of the oxidation reaction, the product was just bubbles of CO2.

 

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Publication Date
Sun Jan 01 2023
Journal Name
The Egyptian Journal Of Hospital Medicine
Changes in Interleukin-35 (IL-35), Anti-TSHR antibody and Human Insulin- like Growth Factor 1 Receptor (IGF1R) in Graves’ Disease Patients Treatedwith Radioactive Iodine
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Publication Date
Fri Sep 01 2023
Journal Name
Journal Of Medicine And Life
Potential anti-obesity effects of two-graded doses of Iraqi <i>Hibiscus tiliaceus</i> leaves extract, alone and in combination with orlistat, on high-fat diet-induced obesity in male rats
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Publication Date
Thu Jan 17 2019
Journal Name
Plant Archives
EFFECT OF ANTI-STRESS ON THE GROWTH AND YIELD OF SWEET AND HOT PEPPERS AND ITS CONTENT OF PEROXIDASE AND IAA
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MS Elias, RGM AL-helfy, Plant Archives, 2019

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Publication Date
Sun Feb 10 2019
Journal Name
Journal Of The College Of Education For Women
Woman’s Identity Crisis in the Clash of Cultures: A Study of Betool Khedairi’s Novel: A Sky So close
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This paper is an attempt to clarify the impact of Postcolonialism, one of the most
challenging fields of study that has emerged in recent years, on representations of women in
once-colonised countries and in Western locations. It discusses the influence of cultural
differences on the status and identity of a woman who experience ‗multiculturalism‘. The
study is an analytical reading of a contemporary novel written by the Iraqi writer Betool Al-
Kudairi. The emphasis lies on the clash between two different cultures and traditions
represented by the British mother and the Iraqi father and its effect on the life and identity of
the protagonist. The main focus is on idea of ‗hybrid identity‘ and the absence of th

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Publication Date
Thu Mar 15 2018
Journal Name
Journal Of Baghdad College Of Dentistry
The Study of Oral Findings, Oxidative Stress and Antioxidant Vitamin E in Serum and Saliva of Crohn's Patients on Azathioprine Monotherapy and those on Combination of Anti-TNF-α Plus Azathioprine
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Background: Crohn's disease (CD) is an immunological disorder associated with chronic inflammatory process of several unspecific regions of gastrointestinal tract but frequently detected in the terminal Ilium and proximal colon or both. This disease frequently presented with various oral manifestations as a consequence of inflammatory process of the disease, nutritional deficiency or medications side effects. Several therapeutic approaches have been developed for CD management that are targeting the inflammatory process and directed at controlling the host immune response. Immunosuppressants such as Azathioprine and anti-TNF α agents as well as the combination of them have been widely used as an effective therapeutic modality with a bett

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Publication Date
Wed Mar 18 2020
Journal Name
Baghdad Science Journal
In Vitro Bioremediation: A Development Process of Cadmium and Mercury Removal by Environmental Biotechnologies of UV-Mutated Escherichia coli K12 and Bacillus subtilis 168
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  1. coli K12 and B. subtilis 168 were investigated for their cadmium and mercury tolerance abilities. They were developed by UV mutagenesis technique to increase their tolerances either to cadmium or mercury, and their names then were designated depend on the name and concentration of metals. E. coli K12 Cd3R exhibited bioremediation amount of 6.5 mg Cd/g dry biomass cell. At the same time, its wild-type (E. coli K12 Cd3) was able to remove 5.2 mg Cd/g dry biomass cell in treatment of 17 mg Cd /L within 72 hours of incubation at 37 °C (pH=7) in vitro assays. The results show that E.coli K12 Hg 20 was able to remove 0.050 µg Hg/g dry biomass cell
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Publication Date
Tue May 28 2024
Journal Name
Plant Science Today
Isolation and identification of hyperin and naringenin from guava cultivated in Iraq and evaluation of cytotoxic activity of hyperin
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The guava plant, Psidium guajava L., serves as proof of the abundant donations of nature, providing a delicious guava fruit; this plant is rich in groups of medicinal and nutritional benefits. Guava belonging to the Myrtaceae family, many previous studies reported many phytochemical constituents in its leaves that have many pharmacological activities and medicinal properties; this study focuses on the isolation, structural elucidation and calculation concentration of flavonoids, assessment of the cytotoxic activityof hyperin from Psidium guajava leaves newly cultivated in Iraq. The isolation process involved the use of thin-layer chromatography (TLC) and preparative high-performance liquid chromatography (PHPLC) and structural eluci

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Publication Date
Mon Mar 01 2021
Journal Name
Journal Of Physics: Conference Series
Evaluation of total oxidant status and antioxidant capacity in sera of acute-and chronic-renal failure patients
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Abstract<p>Renal failure is a disease of the kidney, in which the renal excretory function is failed to process due to depression of the GFR. Renal failure is divided into acute and chronic depending on the period of the disease. The study was designed to investigate the level of oxidative stress in RF patients. Seventy-five subjects had enrolled in the study, who divided into three groups equally, in which they are healthy control, ARF patients, and CRF patients. The results had shown a significant <italic>(P<0.01)</italic> increase in the level of TOS for RF patients when compared with control. Also, a significant difference in the level of TOS has been observed between ARF and CR</p> ... Show More
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Publication Date
Sat Feb 02 2019
Journal Name
Journal Of The College Of Education For Women
The Babylonian Woman As Heroine In Dekker’s Drama: The Babylonian Woman As Heroine In Dekker’s Drama
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Abstract
The present research paper provides an analysis of Thomas Dekker’s
exaltation of the figure of the Babylonian woman as a tragic heroine in his dramatic
art. The paper falls into two sections. The first section outlines the deliberate
mispresentation of the figure of the Babylonian woman in the Bible and the
misreading of that figure. The second section reveals Dekker’s rectification of the
distorted image of the Babylonian woman, whom he defends and glorifies as a
heroine and a victim of misinterpretation and conspiracy.

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