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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 01 2017
Journal Name
Journal Of Al-nahrain University Science
Synthesis and Biological Activity Study of New Some Schiff Bases Derived From D-Erythroascorbic Acid
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Publication Date
Tue Aug 15 2023
Journal Name
Al-academy
The effectiveness of prediction and clairvoyance and its functions in the inner space
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The research dealt with the effectiveness of prediction and foresight in design as a phenomenon that plays a role in the recipient's engagement with the design, as it shows the interaction between the recipient and the interior space. The designer is keen to diversify his formal vocabulary in a way that secures visual values that call for aesthetic integration, as well as securing mental and kinetic behavioral understanding in the interior space.
As the designer deals with a three-dimensional space that carries many visual scenes, the designer should not leave anything from it without standing on it with study and investigation, and puts the user as a basic goal as he provides interpretive data through prediction and foresight that le

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Publication Date
Sun Jun 12 2022
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Effectiveness of Ombitasvir with Paritaprevir/Ritonavir plus Ribavirin on the Treatment of Naïve Patients with Chronic Hepatitis C Virus Genotype 4
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Background Direct-acting antivirals (DAAs) combination therapies from various mechanisms of action and families have been revolutionized the management landscape of chronic hepatitis C virus (HCV). Ombitasvir, paritaprevir with ritonavir (OBV/PTV/r) ± ribavirin (RBV) is approved to treat HCV genotype 4 (GT4) infection. Here, our objective was to delineate the efficacy and safety of OBV/PTV/r plus RBV in treating of Egyptian naïve patients infected with HCV GT4.

Methods a cohort of 100 Egyptian patients infected with HCV GT4 was allocated and administered orally OBV/PTV/r with RBV. The primary endpoint of our study was a sustained virological response (HCV RNA < 12 IU/mL) 12 weeks after the c

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Publication Date
Wed Oct 01 2025
Journal Name
Chinese Journal Of Analytical Chemistry
Synthesis, characterization, antioxidant and bioactivity assessment, and thermodynamic analysis of metal ion complexes using a novel azo dye
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Publication Date
Wed Jun 01 2022
Journal Name
Journal Of The College Of Languages (jcl)
A Feminist Stylistic Analysis of Anti-feminist Poetry in English and Arabic
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Language plays a major role in all aspects of life. Communication is regarded as the most important of these aspects, as language is used on a daily basis by humanity either in written or spoken forms. Language is also regarded as the main factor of exchanging peoples’ cultures and traditions and in handing down these attributes from generation to generation. Thus, language is a fundamental element in identifying peoples’ ideologies and traditions in the past and the present. Despite these facts, the feminist linguists have objections to some of the language structures, demonstrating that language is gender biased to men. That is, language promotes patriarchal values. This pushed towards developing extensive studies to substantiate s

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Publication Date
Wed Dec 15 2021
Journal Name
Al-adab Journal
A Feminist Rhetorical Analysis of Anti-feminist Poetry in English and Arabic
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Publication Date
Thu Mar 09 2017
Journal Name
University Of Baghdad
Synthesis of modified Graphene Oxide and its application as Electrochemical Sensor
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This study involved preparation of Graphene oxide (GO) and reduced graphene oxide (RGO) using Hummer method and chemical method respectively. These carbon nanomaterials were used as starting material to make novel functionalize with thiocarbohydrazide (TCH) which was prepared by reacting CS2 with hydrazine to form GO or RGO- 4-amino,5-substituted 1H,1,2,4 Triazole 5(4H) thion (ASTT) ,(GOT) and( RGOT) respectively via cyclocondensation reaction. Also MnO2 nanorod was prepared to form hybridized with GOT and RGOT. A commercial multiwall carbon nanotube (MWCNT) and functionalization with carboxylic groups' (f-MWCNT) and its nanocomposite with GOT were also prepared. All carbon nanomaterials were characterized with different techniques such as

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Publication Date
Tue Mar 28 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Changes in Serum Levels of Tumor Necrosis Factor-Alpha and Antioxidant status in Different Stages of Malignant Prostate Cancer Patients in Iraq
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Chronic inflammation can induce proliferative events and posttranslational DNA modifications in prostate tissue through oxidative stress. The present study was designed to evaluate the changes in serum levels of TNF-α, malomdialdehyde (MDA) and total antioxidant status (TAS) patients with different stages of malignant prostatic cancer (PCa) and benign prostatic hyperplasia (BPH). One hundred males (age range of 58-72 years) with different stages of malignant PCa were recruited from the Radiotherapy and Nuclear Medicine Teaching Hospital in Baghdad during the period from September 2010 to April 2011. The patients were categorized according to the 4 disease stages (I, II, III, and IV); 25 patients with benign prostatic hyperplasia (BPH)

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Publication Date
Wed May 01 2019
Journal Name
Desalination And Water Treatment
Synthesis and characterization of alumina-grafted acrylic acid monomer and polymer and its adsorption of phenol and p-chlorophenol
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Aluminum oxide (ALO) was grafted by acrylic acid monomer (AlO-AM) and then, it was polymerized to produce alumina grafted poly(acrylic acid) (AlO-AP). The prepared AlO-AM and AlO-AP were characterized by Fourier-transform infrared, differential scanning calorimetry , thermogravemetric analyzer and particle size distribution. Adsorption equilibrium isotherms, adsorption kinetics and thermodynamic studies of the batch adsorption process were used to examine the fundamental adsorption properties of phenol (P) and p-chlorophenol (PCP). The experimental equilibrium adsorption data were analyzed by three widely used two-parameters Langmuir, Freundlich and DubininRadushkevich isotherms. The maximum P and PCP adsorption capacities based on t

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Scopus
Publication Date
Wed Nov 19 2025
Journal Name
Journal Of Baghdad College Of Dentistry
An In Vitro Evaluation of the Effectiveness of Gotu Kola (Centella asiatica) on Inhibiting the Growth of Selected Microorganismsin Human Saliva
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Background: Gotu Kola (Centella asiatica) has been used as a traditional medicine for many years to cure different kinds of diseases. Studies have been reported that Gotu Kola extracts might be used as a cure for oral diseases such as periodontal disease. In the present study, Gotu Kola leaves extracted with water will be used to evaluate its effect on some microorganisms living in the human saliva using minimum inhibitory concentration (MIC) method. Material and Method:Gotu Kola fresh leaves extract have been used with water as a solvent, a rotary evaporator was used to separate the solvent from the extract. The following microorganisms: Streptococci, Lactobacilli, and Staphylococcus aureus have been isolated fromthe Saliva of ten voluntee

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