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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
Sun Jun 02 2019
Journal Name
Journal Of The College Of Languages (jcl)
Artistic Features Of Re-Writing The Novel "On The Eve, on The Eve" By YevgueniBobov: As an Example: Жанровые Особенности Ремейка (На Материале Романа Е. Попова «Накануне Накануне»)
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 The paper tackles two topics. The first is about the term "Ремейк" which is very common in contemporary Russian literature; it has counterparts such as " Обработка" and " Переделка", where these two may indicate any of the following meanings (remake, reformulate, rewrite, treatment, modification, change). It has been shown that this term does not have a stable definition. Also, the role of this term in literary studies has been mentioned along with how it has come to its peak of use in post-modern literature.

The second is that I have taken a sample of well-known works in Russian literature " On the Eve, On the Eve " by the contemporary Russian writer YevgueniBobov, and shown the effort of the writer

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Publication Date
Wed Mar 15 2023
Journal Name
Journal Of Baghdad College Of Dentistry
Anti-inflammatory effects of manuka honey on salivary cytokines (clinical study)
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Background: Manuka honey (MH) is a mono-floral honey derived from the Manuka tree (Leptospermum scoparium). MH is a highly recognized for its non-peroxide antibacterial activities, which are mostly related to its unique methylglyoxal content (MGO) in MH. The beneficial phytochemicals in MH is directly related to their favorable health effects, which include wound healing, anticancer, antioxidant, and anti-inflammatory properties. Aims: The purpose of this study was to evaluate the effect of MH on pro-inflammatory cytokines (IL-8 and TNF-α) in patients with gingivitis and compare it with chlorhexidine (CHX) and distilled water (DW). Materials and Methods: This study was a randomized, double blinded, and parallel clinical trial. Forty-fiv

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Publication Date
Mon Mar 08 2021
Journal Name
Baghdad Science Journal
The micronucleated erythrocytes in speeies of Iraqi fish as indieator of dilution
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The micronucleated erythrocytes in fish was used to detect water pollution by genotoxic agents. Fish belonging to different species were collected from three regions from Baghdad during three months (December/2000,January and February/2001 ).The micronucleated erythrocytes was observed in all the specimens. It was concluded that the genotoxic activity' in one region was less than in die other two regions.?

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Publication Date
Sun Jan 27 2019
Journal Name
Civil Engineering Journal
Prediction of Sediment Accumulation Model for Trunk Sewer Using Multiple Linear Regression and Neural Network Techniques
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Sewer sediment deposition is an important aspect as it relates to several operational and environmental problems. It concerns municipalities as it affects the sewer system and contributes to sewer failure which has a catastrophic effect if happened in trunks or interceptors. Sewer rehabilitation is a costly process and complex in terms of choosing the method of rehabilitation and individual sewers to be rehabilitated.  For such a complex process, inspection techniques assist in the decision-making process; though, it may add to the total expenditure of the project as it requires special tools and trained personnel. For developing countries, Inspection could prohibit the rehabilitation proceeds. In this study, the researchers propos

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Publication Date
Wed Dec 14 2022
Journal Name
Civil Engineering Journal
Rutting Prediction of Hot Mix Asphalt Mixtures Modified by Nano silica and Subjected to Aging Process
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High-volume traffic with ultra-heavy axle loads combined with extremely hot weather conditions increases the propagation of rutting in flexible pavement road networks. Several studies suggested using nanomaterials in asphalt modification to delay the deterioration of asphalt pavement. The current work aims to improve the resistance of hot mix asphalt (HMA) to rutting by incorporating Nano Silica (NS) in specific concentrations. NS was blended into asphalt mixtures in concentrations of 2, 4, and 6% by weight of the binder. The behavior of asphalt mixtures subjected to aging was investigated at different stages (short-term and long-term aging). The performance characteristics of the asphalt mixtures were evaluated using the Marshall s

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Publication Date
Sun Jan 01 2023
Journal Name
2nd International Conference On Mathematical Techniques And Applications: Icmta2021
Antimicrobial activities of some new heterocyclic compounds bearing imidazo[2,1-b]benzothiazole moiety
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Publication Date
Wed Jun 30 2010
Journal Name
Al-kindy College Medical Journal
Human Leukocyte Antigens class II influence the expression of Glutamic Acid Decarboxylase auto antibodies in Type Diabetic children and their Siblings
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Background: The immunogenetic predisposition
may be considered as an important factor for the
development of Type 1 Diabetes Mellitus (T1DM)
in association with the HLA antigens.
Objective:This study was designed to investigate
the role of HLA-class II antigens in the etiology of
type T1DM and in prediction of this disease in
siblings, and its effect on expression of glutamic
acid decarboxylase autoantibodies (GADA).
methods:Sixty children who were newly diagnosed
type 1 diabetes (diagnosed less than five months)
were selected. Their age ranged from 3-17 years.
Another 50 healthy siblings were available for this
study, their ages range from 3-16 years. Eighty
apparently healthy control subjects,

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Publication Date
Wed Mar 12 2025
Journal Name
Journal Of Baghdad College Of Dentistry
Prediction the widths of maxillary and mandibular canines and premolars from the widths of maxillary incisors and first molars (Iraqi study)
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Background: This study aimed to use the combined mesio-distal crowns widths of maxillary incisors and first molars as predictors to the combined mesio-distal crowns widths of maxillary and mandibular canines and premolars. Materials and methods: The sample included 110 Iraqi Arab subjects with an age ranged between 17-25 years and class I skeletal and dental relations. The crown widths of maxillary teeth and mandibular canines and premolars were measured at the largest mesio-distal dimension on the study casts using digital electronic caliper with 0.01 mm sensitivity. Pearson’s correlation coefficient was used to determine the relation between the combined mesio-distal crowns widths of maxillary incisors and first molars and the combined

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Publication Date
Sun Feb 25 2024
Journal Name
Baghdad Science Journal
SBOA: A Novel Heuristic Optimization Algorithm
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A new human-based heuristic optimization method, named the Snooker-Based Optimization Algorithm (SBOA), is introduced in this study. The inspiration for this method is drawn from the traits of sales elites—those qualities every salesperson aspires to possess. Typically, salespersons strive to enhance their skills through autonomous learning or by seeking guidance from others. Furthermore, they engage in regular communication with customers to gain approval for their products or services. Building upon this concept, SBOA aims to find the optimal solution within a given search space, traversing all positions to obtain all possible values. To assesses the feasibility and effectiveness of SBOA in comparison to other algorithms, we conducte

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Publication Date
Tue Apr 18 2023
Journal Name
Corporate Reputation Review
The Absorptive Capacity of Knowledge as an Approach for Building Strategic Reliability in the Sponge Organizations/Small Organizations in Kirkuk Governorate as a Model
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