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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
Thu Feb 26 2026
Journal Name
Research On Crops
Effect of organic acid, amino acids and nano-fertilizer on growth, yield and nitrate concentration of lettuce plant under two farming systems
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Publication Date
Sat Aug 04 2012
Journal Name
University Of Thi-qar Journal
Prediction of Ultimate Soil Bearing Capacity for Shallow Strip Foundation on Sandy Soils by Using (ANN) Techniqu
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Bearing capacity of soil is an important factor in designing shallow foundations. It is directly related to foundation dimensions and consequently its performance. The calculations for obtaining the bearing capacity of a soil needs many varying parameters, for example soil type, depth of foundation, unit weight of soil, etc. which makes these calculation very variable–parameter dependent. This paper presents the results of comparison between the theoretical equation stated by Terzaghi and the Artificial Neural Networks (ANN) technique to estimate the ultimate bearing capacity of the strip shallow footing on sandy soils. The results show a very good agreement between the theoretical solution and the ANN technique. Results revealed that us

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Publication Date
Mon Aug 18 2025
Journal Name
Soil And Sediment Contamination: An International Journal
Remediation Prediction of Contaminated Soil with Crude Oil Using the Optimized Remediation Method for the Iraqi Environment
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Large quantities of petroleum-contaminated soil are generated with increased global energy consumption and crude oil production. This theoretical study evaluates the treatment of 1 ton of petroleum-contaminated soil using seven methods: incineration, physical washing, chemical washing, thermal pyrolysis, Fenton-oxidation-pyrolysis, the biological treatment, and asphaltenes. Data were based on experimental results from the Nahran Bin Omar oil lake in Basra Governorate, Iraq, (2019–2021). The methods were compared by waste generation, treatment cost, and duration. Results indicate that using petroleum-contaminated soil as a raw material for asphalt manufacturing is most beneficial since it is sold as a raw material. Incineration is faster a

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Publication Date
Thu Aug 08 2024
Journal Name
Al-rafidain Journal Of Medical Sciences ( Issn 2789-3219 )
Novel Technique for Alveolar Ridge Expansion: A Comparative Clinical Study
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Background: Piezosurgery improved the split approach by making it safer, easier, and less prone to complications when treating extremely atrophic crests. Densah drills, with their unique design, expand the ridge by densifying bone in a reverse, non-cutting mode. Objective: To assess the effectiveness of sagittal piezosurgery, which involves cutting bone to the full implant depth and then expanding it using osseodensification drills. We use this technique to expand narrow alveolar bones and simultaneously place dental implants in the maxillary and mandibular arches. Methods: Fourteen patients received 31 dental implants. The maxillary arch received 19, and the mandible received 12 dental implants. This study will include patients who

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Publication Date
Mon Nov 25 2019
Journal Name
Alustath Journal For Human And Social Sciences
Barbara Kingsolver: Evaluating Her Contribution to the Eco-Feminist Novel
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Climate change, together with terrorism, economic depressions, and mass-destructive weaponry, is a source of international phobia for many people. The advancement in technology increases the competition among world powers and economic systems to develop their industrial enterprises. The smoke that emits from the factories, the pollution caused by the industrial projects, the excessive use of green gas result in the increase of global warming and have catastrophic effects on the ecosphere of the planet. Besides, man’s wrong practices even in agricultural matters are exhausting the natural resources of the lands, and they badly affect the ecological diversity and the wellbeing of the humans and non-humans alike. Contemporary feminis

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Publication Date
Thu Jan 01 2015
Journal Name
Journal Of Materials Chemistry A
A novel approach to fabricate zeolite membranes for pervaporation processes
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A method has been demonstrated to synthesise effective zeolite membranes from existing crystals without a hydrothermal synthesis step.

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Publication Date
Fri Jan 01 2021
Journal Name
International Journal Of Drug Delivery Technology
Transethosomes a novel transdermal drug delivery system for antifungal drugs
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Publication Date
Thu Feb 01 2024
Journal Name
Baghdad Science Journal
A Novel Gravity ‎Optimization Algorithm for Extractive Arabic Text Summarization
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An automatic text summarization system mimics how humans summarize by picking the most ‎significant sentences in a source text. However, the complexities of the Arabic language have become ‎challenging to obtain information quickly and effectively. The main disadvantage of the ‎traditional approaches is that they are strictly constrained (especially for the Arabic language) by the ‎accuracy of sentence feature ‎functions, weighting schemes, ‎and similarity calculations. On the other hand, the meta-heuristic search approaches have a feature tha

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Publication Date
Thu Oct 01 2020
Journal Name
Defence Technology
A novel facial emotion recognition scheme based on graph mining
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Recent years have seen an explosion in graph data from a variety of scientific, social and technological fields. From these fields, emotion recognition is an interesting research area because it finds many applications in real life such as in effective social robotics to increase the interactivity of the robot with human, driver safety during driving, pain monitoring during surgery etc. A novel facial emotion recognition based on graph mining has been proposed in this paper to make a paradigm shift in the way of representing the face region, where the face region is represented as a graph of nodes and edges and the gSpan frequent sub-graphs mining algorithm is used to find the frequent sub-structures in the graph database of each emotion. T

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Publication Date
Mon Oct 01 2018
Journal Name
Journal Of Economics And Administrative Sciences
Role of the evaluation process of the staff in determining the training programs Field research in the Office of the Inspector General of the Ministry of Health / Iraq
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         The objective of this research is to determine the relationship between the performance evaluation process and the training programs for the employees, to identify the extent of the organization's commitment to perform the performance evaluation process for its employees and to use the results of this process in determining the appropriate training programs. Performance evaluation, functional analysis, evaluation method used, dependent variable (training programs) and its dimensions, type of programs, program objectives, program curriculum, And the application of the field research methodology and the questionnaire, which included 146 individuals to know their views and analyz

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