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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 Mar 12 2025
Journal Name
Journal Of Baghdad College Of Dentistry
Evaluation of olive oil as a separating medium and its effect on some physical properties of processed acrylic resin denture base (A comparative study). Part one
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Back ground: During acrylic resin processing, the mold must be separated from the surface of the gypsum to prevent liquid resin from penetrating into the gypsum, and water from the gypsum seeping into the acrylic resin. For many years, tin foil was the most acceptable separating medium, and because it's difficult to apply, a tin-foil substitute is used. In this study, olive oil is used as an alternative to tin foil separating medium for first time, so the aim of the study was to evaluate its effect as a separating medium on some physical properties such as (surface roughness, water sorption and solubility) of acrylic resins denture base comparing it with those processed using tin-foil and tin foil substitute such as (cold mold seal) separat

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Publication Date
Thu Sep 15 2022
Journal Name
Journal Of Baghdad College Of Dentistry
The push out bond strength of bioceramic seal-er(Total Fill) after warm and cold obturation tech-niques An in vitro comparative
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Background: The goal of a root canal treatment is three dimensional obturation with a complete seal of the root canal system. The aim of this study was to evaluate and compare the effect of two warm obturation techniques, warm vertical compaction (WVC) and, carrier based obturation technique Gutta Core (GC), versus two cold obturation techniques, cold lateral compaction (CLC) and, single cone (SC) on push-out bond strength of bioceramic sealer (Total Fill) at three different root levels. Materials and Methods: Forty extracted maxillary first molars teeth with a straight round palatal root canal and mature apices were selected for this study. After sectioning the palatal roots to 11 mm from the root apex, the canals were prepared wit

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Publication Date
Mon Jan 01 2018
Journal Name
World Journal Of Dentistry
Obturation of Lateral Canals by a New Reciprocating Spreader and a Conventional Finger Spreader by Lateral Condensation Technique: in vitro Comparative Study
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Publication Date
Tue Jan 09 2018
Journal Name
Iraqi Journal Of Cancer And Medical Genetics
Photodynamic Action of low power He-Ne laser on photosensitized human Hep-2 and AMN3 cell lines with Hematoporphyrin derivative in vitro
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Photodynamic Action (PDA) by using appropriate wavelength of irradiation conjugated with porphyrin derivatives is a powerful mechanism of tumor destruction. Hematoporphyrin derivative has been shown to selectively localize in neoplastic cells and then cause destruction of them by generation of singlet oxygen when activated by low power He-Ne laser. Light which used in this study has been emitting from this laser has a wavelength equal to 632.8 nm (red light). Doses of laser had been varied from 3.6 J/cm2 to 14.4 J/cm2 . The beam of laser adjusted with a modified tissue culture plate. Cell lines had exposed to Hematoporphyrin D (HpD) for 24 hours before Laser exposure, their concentrations were varied from 5 µg/ml to 80 µg/ml. Resu

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Publication Date
Thu Sep 15 2022
Journal Name
Journal Of Baghdad College Of Dentistry
The push out bond strength of bioceramic seal-er(Total Fill) after warm and cold obturation tech-niques An in vitro comparative
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Background: The goal of a root canal treatment is three dimensional obturation with a complete seal of the root canal system. The aim of this study was to evaluate and compare the effect of two warm obturation techniques, warm vertical compaction (WVC) and, carrier based obturation technique Gutta Core (GC), versus two cold obturation techniques, cold lateral compaction (CLC) and, single cone (SC) on push-out bond strength of bioceramic sealer (Total Fill) at three different root levels. Materials and Methods: Forty extracted maxillary first molars teeth with a straight round palatal root canal and mature apices were selected for this study. After sectioning the palatal roots to 11 mm from the root apex, the canals were

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Publication Date
Thu Feb 07 2019
Journal Name
Iraqi Journal Of Laser
Antibacterial Photodynamic Effect of 532 nm Diode-Pumped Solid State and 650 nm Diode Lasers on Methicillin Resistant Staphylococcus Aureus in Vitro
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The photodynamic inactivation against Methicillin-resistant Staphylococcus aureus using two different lasers, 532 nm diode pumped solid state laser (DPSS) in combination with safranin O and 650 nm diode laser in combination with methylene blue was investigated in the present work. A hundred swab samples were collected from patients with burn and wound infections admitted to two hospitals in Baghdad (Specialized Burns Hospital in Medical City and Al Imamein Al Jwadein Medical City Hospital) from December 2015 to February 2016 Antimicrobial susceptibility was performed by using Kirby- Bauer method. The irradiation experiments included four groups; a control group, a photosensitizer only group, a laser irradiation only group and a laser irr

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Publication Date
Sun Jan 08 2023
Journal Name
Journal Of Planner And Development
Statistical Evaluation of the Planning Process and Scheduling Management for Irrigation and Drainage Projects in the Republic of Iraq
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The Research aims to investigate into reality in terms of planning and scheduling management process for sake the implementation and maintenance of irrigation and drainage projects in the Republic of Iraq, with an indication of the most important obstacles that impede the planning and scheduling management process for these projects and ways of addressing them and minimizing their effects.                                                  For the purpose of achieving the goal of the research, a sci

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Publication Date
Sun Jun 30 2024
Journal Name
Lark
The Image of the Arab in Hebrew Literature for Young Adults – A Reading of the Novel “Nadia” by Kalila Ron Feder
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يهدف هذا البحث الى التطرق الى صورة العربي كما يعرضها ادب اليافعين العبري في رواية " نادية " للكاتبة العبرية " كاليلا رون فيدر " . والتي تعد من الاديبات العبريات اللواتي تطرقن بصورة مباشرة الى موضوع ما خلف الجدار ، والصراع العربي – الإسرائيلي وانعكاساته على المجتمع الإسرائيلي بصورة عامة والمجتمع العربي بصورة خاصة . ينقسم هذا البحث إلى ثلاثة فصول، تطرق الفصل الأول  إلى "ادب اليافعين"، و تاريخه ، مميزاته والفئ

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Publication Date
Sat Feb 02 2019
Journal Name
Journal Of The College Of Education For Women
The Balance and unbalance in alliance relations The Saudi Arabia and United State Relation as model: The Balance and unbalance in alliance relations The Saudi Arabia and United State Relation as model
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Abstract:
Saudi Arabia and United States long relation could present an important
subject to understand alliance kind in international relations types. We trying
in this study to diagnose and analyze the Saudi Arabia and United States
model to find balance and unbalance statues and its influence on the
directions of Saudi Arabia foreign policy positions.
We divided the study in two parts, each part have many sections. The
first part deal with the historian emergence of Saudi Arabia state and its
development in three stages including its foreign relations with regions and
international powers. While the second part was dedicated in analyzing and
understanding the mechanism and active facts that drawing the Sa

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Publication Date
Thu May 18 2023
Journal Name
Journal Of Engineering
Field Study of Novel Storage Tank of Solar Water Heating System
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In this paper thermo-hydrodynamic characteristics were investigated experimentally for a new type shell-helical coiled tube heat exchanger used as a storage tank of closed loop solar water heater system. Triple concentric helical coils were made of copper tubes of (12.5mm OD and 10mm ID) with coils diameter of (207, 152.2, 97mm) for outer, middle and inner coils respectively. The experiments were carried out during a clear sky days of (March and April 2012). The parameters studied in this work are: history of average temperature of shell side of the storage tank, collector heat gain, heat rejected from coils to shell side of the storage tank, collector efficiency, thermal effectiveness of the heat exchanger (storage tank), and pressure d

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