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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 Dec 05 2023
Journal Name
Baghdad Science Journal
Further Results on (a, d) -total Edge Irregularity Strength of Graphs
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Consider a simple graph   on vertices and edges together with a total  labeling . Then ρ is called total edge irregular labeling if there exists a one-to-one correspondence, say  defined by  for all  where  Also, the value  is said to be the edge weight of . The total edge irregularity strength of the graph G is indicated by  and is the least  for which G admits   edge irregular h-labeling.  In this article,   for some common graph families are examined. In addition, an open problem is solved affirmatively.

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Publication Date
Sun Jan 01 2023
Journal Name
International Journal Of Research In Social Sciences & Humanities
The Effect of Strategic Foresight on Achieving Strategic Entrepreneurship: Applied Research1
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he current research aims to determine the extent of interest of the Oil Products Distribution Company (OPDC) and its various departments in the process of strategic foresight (SF), and the extent of interest that is reflected in the achievement of strategic leadership (SE). As well as knowing the nature of the relationship and the impact on the company. To achieve the objectives of the research, one main hypothesis was formulated, and three sub-hypotheses emerged from it. As the research relied on an analytical survey approach, the research targeted the workers within this company, And he reached a set of results, based on which a number of conclusions were formulated. The research community consisted of (185) individuals, and (160)

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Publication Date
Thu Aug 01 2013
Journal Name
Journal Of The College Of Basic Education
The antimicrobial activity of salvia pratensis extracts against some microbial agent
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The effectiveness inhibitory to extract alcohol for the leaf and flower to plant sage Salvia pratensis each of Staphylococcus aureus, streptococcus epidermidis, Salmonella typhi, Pseudomonas aeroginosa, Escherichia coli, Aspergillus niger and Candida albicans whom had any inhibition to aqueous extracts of the parts itself species bacterial and fungal. The study also demonstrated that the extract of plant containing compounds chemical such as tannins, Alkaloids, Flavonoieds, and saponins, which owns effectiveness of medical. The MIC, MBC and inhibition zones for crud extract were determinated for microbial agents.

Publication Date
Sun Jan 01 2023
Journal Name
Journal Of Interdisciplinary Mathematics
On maps of Γ -period 2 on prime Γ- near-rings
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We present the concept of maps Γ- periodi2 on Γ -near-ring S. Our main goal is to research and explore the presence and mapping traits such as h Γ –hom anti-Γ –hom, Γ –α-derivations of Γ -periodi2 on Γ- near-rings.

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Publication Date
Sun Jan 01 2017
Journal Name
Journal Of Cosmetics, Dermatological Sciences And Applications
Treatment of Recurrent Aphthous Stomatitis by 100% Topical Pumpkin Seed Oil
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Publication Date
Mon Jan 01 2018
Journal Name
Opcion
The effectiveness of using material flow cost accounting to eliminate losses
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This investigation aimed to explain the mechanism of MFCA by applying this method on air-cooled engine factory which was suffering from high production cost. The results of this study revealed that MFCA is a useful tool to identify losses and inefficiencies of the production process. It is found that the factory is suffering from high losses due to material energy and system losses. In conclusion, it is calculated that system losses are the highest among all the losses due to inefficient use of available production capacity.

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Scopus
Publication Date
Fri Nov 01 2013
Journal Name
Journal Of Cosmetics, Dermatological Sciences And Applications
Treatment of active acne vulgaris by chemical peeling using TCA 35%
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KE Sharquie, AA Noaimi, EA Al-Janabi…, Journal of Cosmetics, Dermatological Sciences and Applications, 2013 - Cited by 13

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Publication Date
Wed Jan 01 2020
Journal Name
Periodicals Of Engineering And Natural Sciences
Solving multicollinearity problem of gross domestic product using ridge regression method
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This study is dedicated to solving multicollinearity problem for the general linear model by using Ridge regression method. The basic formulation of this method and suggested forms for Ridge parameter is applied to the Gross Domestic Product data in Iraq. This data has normal distribution. The best linear regression model is obtained after solving multicollinearity problem with the suggesting of 10 k value.

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Scopus
Publication Date
Sat Jan 01 2011
Journal Name
North American Journal Of Medical Sciences
Antagonistic effect of bacteriocin against urinary catheter associated Pseudomonas aeruginosa biofilm
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Publication Date
Fri Jan 01 2021
Journal Name
دراسات قانونية
The Legal Nature of the Build-Operate- transfer-Ownership Contract (B.O.T.)
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The legal nature of the Build-Operate-Transfer-Ownership Contract (B.O.T) The Build, Operate, and Transfer of Ownership Contract (BOT) has emerged as the most successful and safest method for involving the private sector in public sector services. The major infrastructure projects that are built through the BOT contract are no longer financed by the state and its budget, but the private sector has played a major role in financing These projects, especially developing countries that need to establish infrastructure or modernize their existing infrastructure, especially in the areas of transport, communications, services, electricity, water ..... and other public utilities.