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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
Tue Jun 01 2021
Journal Name
Https://www.researchgate.net/journal/iop-conference-series-materials-science-and-engineering-1757-899x
Application of multivariate statistical techniques in the evaluation of large-scale water treatment plants in Baghdad.
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Abstract<p>This paper aims to evaluate large-scale water treatment plants’ performance and demonstrate that it can produce high-level effluent water. Raw water and treated water parameters of a large monitoring databank from 2016 to 2019, from eight water treatment plants located at different parts in Baghdad city, were analyzed using nonparametric and multivariate statistical tools such as principal component analysis (PCA) and hierarchical cluster analysis (HCA). The plants are Al-Karkh, Sharq-Dijlah, Al-Wathba, Al-Qadisiya Al-Karama, Al-Dora, Al-Rasheed, Al-Wehda. PCA extracted six factors as the most significant water quality parameters that can be used to evaluate the variation in drinkin</p> ... Show More
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Publication Date
Sun Mar 01 2020
Journal Name
Baghdad Science Journal
Evaluation of Some Trace Elements Pollution in Sediments of the Tigris River in Wasit Governorate, Iraq
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The main objectives of present study are to evaluate the trace elements pollution in the sediment of the Tigris River and drainage canals in Wasit Governorate, Iraq. Assessment of trace elements pollutants were conducted for 18 sediment samples collected in March 2017. Trace elements were analyzed in sediment Tigris River samples in Wasit Governorate. This metal pollution was evaluated using geo-accumulation (I-geo) index, Contamination Factor (CF) and Pollution Load Index (PLI). According to  these statistical indices, the sediments collected from Tigris River in the study area are highly polluted with Titanium (71.9 ppm), Nickel (226.6 ppm) Chromium (425.2 ppm), Cadmium (2ppm) and Molybdenum (15.8 ppm) while  the sediments&nb

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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
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
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 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
Sun Nov 23 2025
Journal Name
Journal Of Baghdad College Of Dentistry
Evaluation of Andrews' six keys of normal occlusion in a sample of Iraqi adults in Baghdad city
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Background: The Andrews’ six keys of normal occlusion contribute individually and collectively to the total scheme of occlusion and, therefore, are viewed as essential to successful orthodontic treatment. The present research aims to evaluate the presence of the parameters of the Andrews’ Six Keys of normal occlusion in a sample of 100 Iraqi adults with complete permanent dentition and clinically acceptable normal occlusion (Angle’s Class I) in Baghdad city. Their age range 18-25 years (60 males and 40 females). Materials and methods: Each patient was subjected to clinical examination and then study cast models were made, with their occlusal records. The measuring tools that have been used involved: Three-dimensional goniometer to me

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Publication Date
Mon Feb 01 2021
Journal Name
Journal Of The College Of Languages (jcl)
The Broken Wings: The character of the Arab Christian |Woman in Sami Michael's Novel "Trumpet in the Wadi" versus "Jasmine" by Eli Amir
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Sami Michael and Eli Amir - two Israeli writers born in Iraq and of the same generation (Sami Makhail was born in Baghdad in 1926 and Eli Amir in 1937). They wrote in their novels, among other things, about Orientalism , love and femininity. They both lived wild, extroverted lives. They did not shy away from experiencing anything new that came their way, rebelled against conventions and acted provocatively; they enjoyed the shock and amazement that evoked around them. While trying to find their place in different family settings, they chose to present two Arab Christian heroines. The narrator in Jasmine is the speaker Noori-Eli himself. While the narrator of “Trumpet in the Wadi” is Huda the heroine herself. Both are independent and bot

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