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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
Sat Jul 01 2023
Journal Name
The Egyptian Journal Of Hospital Medicine
Evaluation of the Antibiofilm Activity of Laurus nobilis Leaves Extract and Assessment of Its Effect on fimA and papC genes in Escherichia coli isolates
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Background: The beneficial gut bacterium E. coli can cause blood poisoning, diarrhoea, and other gastrointestinal and systemic disorders. Objective: This study amid to examines the antibiofilm activity of Laurus nobilis leaves extract on E. coli isolates and compares pre- and post-treatment gene expression of fimA and papC genes. Subjects and Methods: Ten isolates of E. coli were obtained from the Genetic Engineering and Biotechnology Institute, University of Baghdad, which was previously collected from Baghdad city hospitals and diagnosed by chemical tests, the diagnosis was confirmed using VITEK-2 System. The preparation of the aqueous and methanolic Laurus nobilis leaves extracts was done by using the maceration method and Soxhlet appara

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Publication Date
Sat Jul 01 2006
Journal Name
Saudi Medical Journal
Treatment of alopecia areata by topical diclofenac sodium gel in comparison to benzoyl peroxide gel. A novel single blind therapeutic clinical trial
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KE Sharquie, AA Al-Nuaimy, WJ Kadhum, Saudi medical journal, 2006 - Cited by 3

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Publication Date
Tue Dec 09 2025
Journal Name
Journal Of Computer-aided Molecular Design
Synthesis, characterization and density functional theory of a novel dichloro(2-(1-anthracene-9-ylmethyl)-1H-1,2,3-triazole-5-yl) pyridine)Cu(II) and polymeric dichloro(2-(1-anthracene-9-ylmethyl)-1H-1,2,3 -triazole-5-yl)pyridine) Cd(II) complexes
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Publication Date
Tue Apr 30 2024
Journal Name
The Iraqi Geological Journal
Evaluation of Heavy Metals Pollution in the Sediments of Diyala River Lower Reaches, Eastern Iraq
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 Investigating the heavy metals in soil is important to the life of humans and living organisms. Diyala River Lower Reaches was chosen due to the changes in environmental characteristics that took place in recent years. Twelve sediment samples were collected from four different sites. The physical, and chemical properties and the concentrations of nine heavy metals were indicated. The results showed that the average concentrations of arsenic, copper, chromium, cobalt, iron, manganese, nickel, lead, and zinc are 8.5, 45.7, 538.5, 12.2, 5.07, 991.7, 183.5, 16.07, 136.5 ppm, respectively. They reflect contamination with arsenic, chromium, and nickel, while they are free of lead, and zinc contamination, according to the Environmental P

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Publication Date
Tue Dec 13 2011
Journal Name
Iraqi Journal Of Laser
Evaluation of Low Level Laser Therapy Using Diode Laser in Enhancement of Episiotomy Wound Healing
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we studied the effect of low level laser therapy (LLLT) using diode laser with wavelength of (790-805) nm in promotion and enhancement of wound healing of episiotomy and to evaluate the analgesic effect of LLLT in reducing the pain sensation caused by the episiotomy wounds. Nineteen women with episiotomy wound were selected and divided into three groups; 1st group (group No.1: control group) given antibiotics without laser therapy, in the 2nd group (group No.2) the wounds were exposed to laser therapy (4 sessions, each session with energy density of 19.90 J /cm2 every other day ) and systemic antibiotics were prescribed for 1 week. In the 3rd group (group No.3) the wounds were exposed to laser therapy (4 sessions, the same as in the 2nd

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Publication Date
Tue Jan 01 2019
Journal Name
Malaysian Journal Of Biochemistry & Molecular Biology
Evaluation influence of extract of Terfezia claveryi desert truffle, pezizaceae, against Streptococcus pneumoniae, in vivo
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Publication Date
Thu May 31 2012
Journal Name
Journal Of Baghdad College Dentistry
An evaluation of water absorption of Giomer in comparison to other resin-based restorative materials
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Background: Polymeric composites have been widely used as dental restorative materials. A fundamental knowledge and understanding of the behavior of these materials in the oral cavity is essential to improve their properties and performance. The goal of this study was to measure water sorption of four composite resins containing different filler and resin matrix contents. Materials and method: Resin composite specimens giomer (Beautifil II) Filtek™ P90, Filtek™ Z350 XT, and Tetric N Ceram were prepared in a cylindrical mould of 3mm thickness and 6mm diameter (n=10) and light cured . All specimens placed in silica-gel desiccators at 37˚C for seven days, a constant weight was obtained. All samples were immersed in deionized distill

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Publication Date
Sun Aug 01 2021
Journal Name
Journal Of Education And Science
Evaluation of Salivary Alpha-Amylase level in Iraqi children with positive family history of hypertension
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This study accomplished to determine levels of salivary Alpha-Amylase (sAA) in Iraqi children with positive family history of hypertension, Hypertension was believed to be a risk factor in 18% of all deaths in 2010 (9.4 million globally). This study included one hundred children from primary school aged 6 to 13 years, with a focus in child welfare and family health history, with an emphasis on close relatives' hypertension reputations, with hypertension close relatives record categories identified by 1st and 2nd relatives, after documenting the full details, the burden was assessed for the children's families. The influence of age is confirmed by a correlation study of our own numbers, which shows a positive correlation. The disparity betwe

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Publication Date
Wed Sep 14 2016
Journal Name
Journal Of Baghdad College Of Dentistry
Histological Evaluation of Effect of beta-Tricalcium Phosphate on Bone healing in Alloxan-Induced diabetes
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Background: Improved glucose level control with insulin injections have allowed for the diabetic population to live longer and healthier lives. Unfortunately diabetes remains a worldwide epidemic disease with multiple health implications. Specifically, its effects upon fracture healing are compromised in diabetics with as high as 87% recovery delay relative to “healthy” counterparts. Current medical treatments for bone injuries have been largely focused on replacing the lost bone with allogenic or autogenous bone grafts, beta-tricalcium phosphate (β -TCP), a ceramic alloplast, has interconnected system of micropores, has been widely used as a biologically safe osteoconductive bone substitute. The aim of this study was histol

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Publication Date
Fri Feb 17 2023
Journal Name
Sustainability
Sustainable Utilization of Machine-Vision-Technique-Based Algorithm in Objective Evaluation of Confocal Microscope Images
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Confocal microscope imaging has become popular in biotechnology labs. Confocal imaging technology utilizes fluorescence optics, where laser light is focused onto a specific spot at a defined depth in the sample. A considerable number of images are produced regularly during the process of research. These images require methods of unbiased quantification to have meaningful analyses. Increasing efforts to tie reimbursement to outcomes will likely increase the need for objective data in analyzing confocal microscope images in the coming years. Utilizing visual quantification methods to quantify confocal images with naked human eyes is an essential but often underreported outcome measure due to the time required for manual counting and e

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