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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 Jan 03 2017
Journal Name
World Journal Of Experimental Biosciences
Effect of Soil Extracts on Ability of Clinical Isolates of Pseudomonas aeruginosa and Staphylococcus aureus to Produce Biofilm in vitro
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In present study the effect of soil extracts of different types of soil on ability of two clinical isolates, Pseudomonas aeruginosa and Staphylococcus aureus to form biofilm. The extract of soil was done by using sterile phosphate buffer saline and analyzed by Fourier Transform Infrared Spectroscopic (FTIR). Spectrophotometric method was used to check ability of the studied isolated bacteria to form biofilm on polystyrene microtiter plates. The data of FTIR showed very little difference was observed among extracts of three types of soil (soil contaminated with hydrocarbons; garden soil collected from gardens of al-jadrea, Baghdad and containers soil), but the highest difference was observed in the extract obtained from peat moss clay soil.

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Publication Date
Wed Jan 01 2003
Journal Name
Ipmj-iraqi Postgraduate Medical Journal
Changes in acid phosphatase activity in rat’s mammary tissue from virginity, through pregnancy, lactation and post–lactation
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Purpose: Studying the activity of acid phosphatase, which is the marker of lysosomal activity in the mammary glands of rats at different stages of the physiological maturation [virgih, pregnancy, lactation and Post lactation] Methods: Forty, female, albino rats were used in this study. They were divided into four groups according to their physiological states [virgin, pregnancy, lactation and post lactation]. The mammary glands, after suitable fixation and sectioning, were employed for routine haematoxylin and eosin stain and for acid phosphatase demonstration Results: Acid phosphatase activity was weakly diffuse in the secretory tubules of virgin rats, the diffuse and granular activity of this enzyme was increased during pregnancy in the s

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Publication Date
Wed Mar 10 2021
Journal Name
Baghdad Science Journal
Effect of (1,4) phenylenediamine on the corrosion of lead in 1M hydrochloric acid solution
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The accelerating effect of 1,4- phenylenediamine (PDA) additions in 1M hydrochloric acid solution at temperature rang (20-60) C° has been studied by weight losses measurement during ranging time (1-260) h and by following the pb2+ concentration in solution after several times by using Atomic absorption spectroscopy (AAS) . The volume of hydrogen gas involving was followed also in presence and absence of (PDA) in the corrosive solution .Accelerating enhanced by adding (NaCl , NaBr , NaI ) was also investigated.

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Publication Date
Mon May 02 2022
Journal Name
International Journal Of Research In Social Sciences & Humanities An International Open-access Peer Reviewed Referred Journal
Identity Construction and Social Structures in Sia Figiel’s Novel Where We Once Belonged
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This article focuses on identity construction and social structures within the Sāmoan community as represented in Sia Figiel’s novel Where We Once Belonged. I argue that however the post/colonial Sāmoan identity is hybridized, the essence of the individual is still connected to Fa’a Sāmoa-the Sāmoan traditions and ways. However rapid are the colonial vicissitudes, the Sāmoan literature and lifestyle are developed to be a resistance platform. This resistance platform is dedicated not only to expose the colonial impact but also to assist the social and political reconstruction of post/colonial Samoa. To this end, this article studies identity construction, and the challenges that women face within Sāmoan social structures.

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Publication Date
Wed Jan 01 2025
Journal Name
Modern Sport
Vertical Resistance and Its Relationship with Speed-Strength and Biomechanical Variables During the Takeoff Phase and the Performance of Selected Activities in Individual and Team Sports
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Jumping ability is a fundamental variable in many sports, as its execution requires an integration of muscular strength Q1 and certain biomechanical variables. This is particularly evident in gymnastics jumping events and jump shots in ball games, both of which rely on a high level of vertical resistance. Vertical resistance serves as an indicator of an athlete’s ability to overcome their body weight while counteracting gravitational force to achieve optimal performance. As such, it is considered one of the key factors in movements that demand explosive power and speed. The researchers believe that despite the significant relationship between vertical resistance, speed-strength of the arms and legs, and certain biomechanical varia

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Publication Date
Sat Jul 09 2022
Journal Name
Multidisciplinary International Journal
Fostering of Iraqi EFL Teachers towards Activities Teaching Literature
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This study intends to look into the activities instructors use in the classroom to teach literature. Three models for teaching literature were added into the study in order to deepen the use of activities in the classroom. They are six activities in the teaching of literature were listed as indicators investigated during the study; language based, paraphrastic, information-based, personal response, moral-philosophical, and stylistic. An emphasizing the teaching of literature, the classroom activities used were mostly concentrated on the technical aspects of reading, writing, listening, and speaking. Through observing the classroom, it was revealed that teachers employed more Language-Based activity, Moral-Philosophical activity, and Informa

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Publication Date
Tue Feb 01 2022
Journal Name
Baghdad Science Journal
Milk Tumor Necrosis Factor Alpha and Interleukin-1Beta Among Toxoplasma gondii-Free and Infected Women
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Pro-inflammatory cytokines play an important role in intercellular communications. In the last two decades, many cytokines have been identified in human milk. These cytokines are variable according to different conditions such as pathogenic infections which strongly stimulated the immune response. The present study aims to determine of IL1β and TNF-α in Toxoplasma gondii-free and infected women in an attempt to clarify the impacts of the infections on cytokines especially in mother's milk. The serum and milk sample were collected from 96 samples (48 for seropositive and 48 for seronegative). To confirm the Toxoplasma gondii infection; enzyme linked immunofluorescence assay (ELIFA) was used to detect anti-Toxoplasma Ig

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Publication Date
Sun Jul 26 2026
Journal Name
Journal Of Baghdad College Of Dentistry
The Effect of Zinc Oxide Nanoparticles on Streptococcus mutans of Human Saliva (In Vitro Study)
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Background: Nanotechnology represents a new science that promises to provide a broad range of uses and improved technologies for biological and biomedical applications. One of the reasons behind the intense interest is that nanotechnology permits synthesis of materials that have structure is less than 100 nanometers. The present work revealed the effect of zinc oxide nanoparticles (ZnO NPs) on Streptococcus mutans of Human Saliva in comparison to de-ionized water. Materials and methods: Streptococcus mutans were isolated from saliva of forty eight volunteers of both sexes their age range between 18-22 years and then purified and diagnosed according to morphological characteristic and biochemical tests. Different concentrations of ZnO NPs w

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Publication Date
Wed Jan 01 2014
Journal Name
The Scientific World Journal
An In Vitro Assessment of Gutta-Percha Coating of New Carrier-Based Root Canal Fillings
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The first aim of this paper was to evaluate the push-out bond strength of the gutta-percha coating of Thermafil and GuttaCore and compare it with that of gutta-percha used to coat an experimental hydroxyapatite/polyethylene (HA/PE) obturator. The second aim was to assess the thickness of gutta-percha around the carriers of GuttaCore and HA/PE obturators using microcomputed tomography (μCT). Ten (size 30) 1 mm thick samples of each group (Thermafil, GuttaCore, and HA/PE) were prepared. An orthodontic wire with a diameter of 0.5 mm was attached to the plunger of an Instron machine in order to allow the push-out testing of the gutta-percha coating. Five samples of (GuttaCore and HA/PE) were scanned using

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Publication Date
Mon Aug 22 2016
Journal Name
Journal Of Natural Sciences Research
In Vitro Cytotoxic Effect of Aqueous Extract of Origanum Marjoram on AMN-3 Cell Line
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