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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 Jan 25 2018
Journal Name
International Journal Of Current Engineering And Technology
Model-Based Design of Piezoelectric Patches used to Repair Damaged Beams under Static Load
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Static loads exposing to mechanical components can cause cracks, which are lead to form stress concentration regions causing the failure of structure. Generally, from 80% to 90% of structure failure is due to initiation of the cracks. Therefore, it is necessary to repair the crack and reduce its effect on the structure where the effect of the crack is modelled as an additional flexibility to the structure. In the last few years, piezoelectric materials have been considered as one of the most favourable repairing techniques. The piezoelectric material converts the applied voltage on it to a bending moment to counter the bending moment caused by the external load on the beam at the crack location. In this study, the design of the piez

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Publication Date
Wed Mar 01 2023
Journal Name
Accounting And Financial Sciences Journal
The Extent to which the Quality of Accounting Information Systems Contributes to Reducing Material
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This research dealt with shedding light on the nature of material misrepresentations, in addition to knowing the extent to which the quality of accounting information systems contributes to reducing material misrepresentations On the theoretical side, a number of sources were relied upon in dealing with the research problem and presentation of the topic, while in the practical side, it was relied on the questionnaire form, where the research sample was (accountants and auditors), where 50 forms were distributed and 50 were received, and the data was analyzed and hypotheses tested through the program Statistical spss to show the relationship between the variables. The research reached a number of conclusions, the most important of which is t

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Publication Date
Thu Jul 01 2010
Journal Name
International Journal Of Advancements In Computing Technology
Implementation of digital chaotic signal generator based on reconfigurable LFSRs for multiple access communications
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This paper describes the digital chaotic signal with ship map design. The robust digital implementation eliminates the variation tolerance and electronics noise problems common in analog chaotic circuits. Generation of good non-repeatable and nonpredictable random sequences is of increasing importance in security applications. The use of 1-D chaotic signal to mask useful information and to mask it unrecognizable by the receiver is a field of research in full expansion. The piece-wise 1-D map such as ship map is used for this paper. The main advantages of chaos are the increased security of the transmission and ease of generation of a great number of distinct sequences. As consequence, the number of users in the systems can be increased. Rec

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Scopus
Publication Date
Sun Feb 03 2019
Journal Name
Journal Of The College Of Education For Women
Solution of the electromechanical machining problem using the collocation method based on Bernstein polynomials
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Publication Date
Sun Jan 01 2023
Journal Name
Ssrn Electronic Journal
Design of Earthquake-Resistant Buildings by Using Reinforced Concrete or Steel Flexible Corner Joints
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This study focuses on studying the effect of reinforced steel in detail, and steel reinforcement (tensile ratio, compression ratio, size, and joint angle shape) on the strength of reinforced concrete (compressive strength) Fc' and searching for the most accurate details of concrete divisions, their behavior, and corner resistance of reinforced concrete joint. The comparison of this paper with previous studies, especially in the studied properties. The conclusions of the chapter are summarized that these effects had a clear effect and a specific effect on the behavior and resistance of the reinforced concrete corner joints under the negative moments and under their influence and the resulting stress conditions. The types of defects that can

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Publication Date
Tue Jun 01 2021
Journal Name
Baghdad Science Journal
A New Methodology to Find Private Key of RSA Based on Euler Totient Function
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          The aim of this paper is to present a new methodology to find the private key of RSA. A new initial value which is generated from a new equation is selected to speed up the process. In fact, after this value is found, brute force attack is chosen to discover the private key. In addition, for a proposed equation, the multiplier of Euler totient function to find both of the public key and the private key is assigned as 1. Then, it implies that an equation that estimates a new initial value is suitable for the small multiplier. The experimental results show that if all prime factors of the modulus are assigned larger than 3 and the multiplier is 1, the distance between an initial value and the private key

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Publication Date
Sat Mar 30 2019
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Estimation of rock strength from sonic log for Buzurgan oil field: A Comparison study
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It is very difficult to obtain the value of a rock strength along the wellbore.  The value of Rock strength utilizing to perform different analysis, for example, preventing failure of the wellbore, deciding a completion design and, control the production of sand.  In this study, utilizing sonic log data from (Bu-50) and (BU-47) wells at Buzurgan oil field.  Five formations have been studied (Mishrif, Sadia, Middle lower Kirkuk, Upper Kirkuk, and Jaddala) Firstly, calculated unconfined compressive strength (UCS) for each formation, using a sonic log method.  Then, the derived confined compressive rock strengthens from (UCS) by entering the effect of bore and hydrostatic pressure for each formation.  Evaluations th

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Publication Date
Fri Sep 01 2017
Journal Name
Journal Of Engineering
Fire Flame Influence on the Behavior of reinforced Concrete Beams Affected by Repeated Load
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The influence and hazard of fire flame are one of the most important parameters that affecting the durability and strength of structural members. This research studied the influence of fire flame on the behavior of reinforced concrete beams affected by repeated load. Nine self- compacted reinforced concrete beams were castellated, all have the same geometric layout (0.15x0.15x1.00) m, reinforcement details and compressive strength (50 Mpa). To estimate the effect of fire flame disaster, four temperatures were adopted (200, 300, 400 and 500) oC and two method of cooling were used (graduated and sudden). In the first cooling method, graduated, the tested beams were leaved to cool in air while in the second method, sudden, water splash was use

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Publication Date
Thu Jan 23 2020
Journal Name
Iraqi Journal Of Laser
Assisted Non-Surgical Therapy of Periodontal Pockets Utilizing Diode Laser: A Randomized Clinical Trial
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Periodontal diseases are inflammatory diseases, for which, scaling and root planning is the main approach. Diode laser therapy as an adjunct to non-surgical periodontal treatment has shown some beneficial effects.

Aim: The objective of this single randomized controlled clinical study was to assess the effect of a 940 nm diode laser as an adjunct to SRP therapy in the treatment of periodontal pockets.

 Methods: In this study, twenty patients in need of periodontal treatment with periodontal pocket ≥ 4 mm were selected for this split-mouth clinical study. Test group treated by diode laser 940 nm as an adjunct with SRP, control group treated by SRP in contralateral quadrants. Clinical

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Publication Date
Tue Mar 02 2021
Journal Name
Humanitarian And Natural Sciences Journal
THE LINGUISTIC STRUCTURES OF THE HISTORIANS ALYAQOUBI (284 AH / 897 AD) ARE A MODEL
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The research in the linguistic structures of the historians Al-Yaqoubi is considered a model of the important topics in historical studies in general, given its importance in the lives of peoples due to its connotations and meanings that summarize interpretation, clarification, and prolonged speech, as it includes life meanings with many dimensions, these structures have been used in historical incidents Important, and throughout the different ages, as it can be used to support an opinion, solve problems, prove evidence, increase wisdom, and it needs rich life experiences, and a sound language, to use it, and needs a wide absorptive capacity for the recipient, the research included linguistic structures in the achievement of science , Lingu

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