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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 Apr 01 2020
Journal Name
Brazilian Dental Journal
In Vitro Homeostasis of Rat Oral Epithelial Cell Cultures Following Withdrawal of Periodontal Pathogens
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Abstract Inflammation of periodontal tissues is the consequence of interaction between periodontal pathogens and immune system. This is associated with increased expression of inflammatory cytokines, which may exert destructive effect to the periodontal tissues when released over long period. The aim of this study was to chronologically track the homeostasis of oral keratinocytes following removal of periodontal pathogens. This was done by investigating expression of selected inflammatory markers and integrity of epithelial monolayers in vitro. Rat oral keratinocytes were stimulated with heat-killed Fusobacterium nucleatum and Porphyromonas gingivalis over 7-days then bacteria were washed away and epithelial cells re-cultured for 3-

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Publication Date
Sun Jul 26 2026
Journal Name
Journal Of Baghdad College Of Dentistry
The effects of different concentrations of Alum solutions on Mutans streptococci (in vitro study)
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Background: Alum has been used as a treatment medication in cases of oral and gingival ulcers, and also as antiseptic mouthwash. This study aimed to examine the effects of different concentrations of Alum on inhibition zone, viability counts and adherence ability of Mutans streptococci compared with deionized water and chlorhexidine gluconate in vitro. Materials and methods: The study dealt with an in vitro study to establish a concentration of Alum mouthrinse that would have the minimum inhibitory concentration and minimum bacteriocidal concentration. The second part evaluated the anti-adherence ability of the experimental agents. Results: This study found that the antibacterial effect of Alum increases with its concentration from 50 to 1

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Publication Date
Mon Jan 01 2007
Journal Name
Iraqi Postgraduate Medical Journal
Therapeutic evaluation of spironolactone and finasteride in the treatment of acne vulgaris
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S Khalifa E, AM Sabeeh A, AN Adil A, AW Ghassan H…, 2007

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Publication Date
Thu Mar 31 2016
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Corrosion Inhibition of Low Carbon Steel in Sulfuric Acid Using Polyvinyl Alcohol
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The inhibitive power of Polyvinyl Alcohol (PVA) was investigated toward the corrosion of carbon steel in 0.2N H2SO4 solution in the temperature range of 30-60˚C and PVA concentration range of 150-2000 ppm.

   The corrosion rate was measured using both the weight loss and the electrochemical techniques. The weight loss results showed that PVA could serve as a corrosion inhibitor but its inhibition power was found to be low for the corrosion of carbon steel in the acidic media. Electrochemical analysis of the corrosion process of carbon steel in an electrochemical corrosion cell was investigated using 3-Electrode corrosion cell. Polarization technique was used for carbon steel corrosion in 0.2N H

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Publication Date
Fri Sep 30 2011
Journal Name
Journal Of Electrochemical Science And Technology
Electrodeposition of Silicon from Fluorosilicic Acid Produced in Iraqi Phosphate Fertilizer Plant
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Publication Date
Sat Jun 01 2019
Journal Name
Prensa Medica Argentina
The effect of niclosamide in acetic-acid induce colitis: An experimental study
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Publication Date
Thu Mar 07 2024
Journal Name
Oncology Letters
Effect of valproic acid on histone deacetylase expression in oral cancer (Review)
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Publication Date
Sat Mar 25 2023
Journal Name
International Journal Of Drug Delivery Technology
The Protective Eff ect of Cinnamic Acid against Ulcerative Colitis in Mice
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Objective: To study the protective eff ects of cinnamic acid on dextran sodium sulfate (DSS) induced ulcerative colitis (UC) in mice. Materials and methods. Forty adult male mice were randomLy divided into fi ve groups, control group, an induction group received 3% DSS in drinking water for 7 consecutive days. Two treatment groups received oral suspension of cinnamic acid 50 and 25 mg/kg, respectively and 3% DSS in drinking water, for 7 consecutive days. The fi nal group received oral suspension of cinnamic acid 50 mg/kg for the latter 7 days without DSS in drinking water. All the animals were euthanized on day eight. The colon of animals was extracted and divided into two sections, the middle was homogenized and biochemically analy

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Publication Date
Mon May 01 2023
Journal Name
Journal Of Medicine And Life
Mucoprotective effect of ellagic acid in 5 fluorouracil-induced intestinal mucositis model
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Publication Date
Sat May 01 2021
Journal Name
Journal Of Engineering
A Prediction Formula for The Estimation of Sediment Load in The Upper Reach of Al-Gharraf River
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The presence of deposition in the river decreases the river flow capability's efficiency due to the absence of maintenance along the river. In This research, a new formula to evaluate the sediment capacity in the upstream part of Al-Gharraf River will be developed. The current study reach lies in Wasit province with a distance equal to 58 km. The selected reach of the river was divided into thirteen stations. At each station, the suspended load and the bedload were collected from the river during a sampling period extended from February 2019 till July 2019. The samples were examined in the laboratory with a different set of sample tests. The formula was developed using data of ten stations, and the other three s

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