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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
Wed May 01 2019
Journal Name
Iraqi Journal Of Science
In Vitro Regeneration of Pimpinella anisum L. Using Different Plant Growth Regulators
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Plant regeneration protocols were developed for medicinally important anise (Pimpinella anisum L.) that successfully achieved from seeds. Seeds were sterilized and inoculated on Murashige and Skoog (MS) medium with and without gibberellins (GA3) until full germination. The highest percentage of germination (100%) was recorded on MS medium treated with 2.0 mg/L GA3 after 7 days. For shoot proliferation, different concentrations of 6- benzyl adenine BA (1, 1.5, 2 mg/L) were used. To enhance shoot induction, 0.1 mg/L of naphthalene acetic acid (NAA) and 0.01 mg/L of thidiazuron (TDZ) were tested along with BA. Direct regenerated shoots were obtained on MS medium supplemented with BA alone (2mg/L) which gave (7shoot/explant), while the presence

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Publication Date
Sat Oct 30 2021
Journal Name
Iraqi Journal Of Science
The Effects of Conductance on Metastable Switches in Memristive Devices Based on Anti-Hebbian and Hebbian (AHaH) Learning Rules
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     In the last few years, the literature conferred a great interest in studying the feasibility of using memristive devices for computing. Memristive devices are important in structure, dynamics, as well as functionalities of artificial neural networks (ANNs) because of their resemblance to biological learning in synapses and neurons regarding switching characteristics of their resistance. Memristive architecture consists of a number of metastable switches (MSSs). Although the literature covered a variety of memristive applications for general purpose computations, the effect of low or high conductance of each MSS was unclear. This paper focuses on finding a potential criterion to calculate the conductance of each MMS rather t

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Publication Date
Sat Oct 30 2021
Journal Name
Iraqi Journal Of Science
The Effects of Conductance on Metastable Switches in Memristive Devices Based on Anti-Hebbian and Hebbian (AHaH) Learning Rules
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     In the last few years, the literature conferred a great interest in studying the feasibility of using memristive devices for computing. Memristive devices are important in structure, dynamics, as well as functionalities of artificial neural networks (ANNs) because of their resemblance to biological learning in synapses and neurons regarding switching characteristics of their resistance. Memristive architecture consists of a number of metastable switches (MSSs). Although the literature covered a variety of memristive applications for general purpose computations, the effect of low or high conductance of each MSS was unclear. This paper focuses on finding a potential criterion to calculate the conductance of each M

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Publication Date
Thu Sep 08 2022
Journal Name
Al-khwarizmi Engineering Journal
Performance Prediction in EDM Process for Al 6061 Alloy Using Response Surface Methodology and Genetic Algorithm
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The Electric Discharge (EDM) method is a novel thermoelectric manufacturing technique in which materials are removed by a controlled spark erosion process between two electrodes immersed in a dielectric medium. Because of the difficulties of EDM, determining the optimum cutting parameters to improve cutting performance is extremely tough. As a result, optimizing operating parameters is a critical processing step, particularly for non-traditional machining process like EDM. Adequate selection of processing parameters for the EDM process does not provide ideal conditions, due to the unpredictable processing time required for a given function. Models of Multiple Regression and Genetic Algorithm are considered as effective methods for determ

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Publication Date
Wed Aug 11 2021
Journal Name
Nauchforum
ROLE OF METAPHOR IN PUPPET IMPLEMENTATION (ON THE EXAMPLE OF D. RUBINA'S NOVEL «PETRUSHKA'S SYNDROME»)
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The article examines metaphors as one of the fundamental means used by D. Rubina when writing the novel “Parsley Syndrome” to form images of dolls as equal heroes of the work. The author of the article continues research related to the work of Dina Ilinichna Rubina, a representative of modern Russian prose.

Publication Date
Tue Sep 08 2020
Journal Name
Baghdad Science Journal
A Study of Apelin-36 and GST Levels with Their Relationship to Lipid and Other Biochemical Parameters in the Prediction of Heart Diseases in PCOS Women Patients
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This work studies the role of serum apelin-36 and Glutathione S-transferases (GST) activity in association with the hormonal, metabolic profiles and their link to the risk of cardiovascular disease (CVD) in healthy and patients' ladies with polycystic ovary syndrome (PCOS). A total of fifty-four (PCOS) patients and thirty-one healthy woman as a control have been studied. The PCOS patients were subdivided on the basis of body-mass-index (BMI), into 2-subgroups (the first group was obese-PCOS with BMI ≥ 30 and the second group was non-obese PCOS MBI<30). Fasting-insulin-levels and Lipid-profile, Homeostatic-model assessment-of-insulin-resistance (HOMA-IR), follicle-stimulating-hormone (FSH), luteinizing-hormone (LH), testosterone and

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Publication Date
Tue Aug 01 2017
Journal Name
Iosr Journal Of Dental And Medical Sciences (iosr-jdms)
Is deferasirox As Effective As Desferrioxamine in Treatment of Iron Overload In Patients With Thalassemia Major?
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Publication Date
Mon Mar 08 2021
Journal Name
Baghdad Science Journal
Synthesis and Characterization of N-((6-substituted - Benzothiazol-2-Y)succunamic acid.3-(6-substituted-benzothiazol-2-Y1)-Carbamoyl Prorionyl Chloride and study of thier Biological effects
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Twelve N-(6-sustirured benzothanol-2-y1) succinamic acids and 3-(6-substitted benzonathol-2-y1)-carbamoyl propionyl chloride were synthesized in good yields from reaction of benzonathol2-yl)

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Publication Date
Thu Apr 29 2021
Journal Name
Iraqi Journal Of Science
Speculative Carcinogenicity Assessment of Polycyclic Aromatic Hydrocarbons Found in Some Anti-Diarrheal Herbal Drugs Sold in Ondo State of Nigeria
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The conviction that herbal drugs have enormous health benefits has led to increase the rate of their consumption by Nigerians. The aim of this study was to assess the carcinogenic property of some popularly consumed anti-diarrheal herbal drugs via polycyclic aromatic hydrocarbons (PAHs) quantification. Three prevalent anti-diarrhea herbal drugs , Odunmo herbal drug (Hibiscus rosa-sinensis and Bacopamonnieri), Orogun herbal mixture (Hibiscus sabdariffaI and Hedera helix), and Alora herbal syrup (Aloe vera and Hibiscus sabdariffaI) were bought for the purpose of this study and they were coded as samples A, B, and C, respectively. The ultrasonic extraction of the herbal drugs was carried

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Publication Date
Mon Jul 31 2023
Journal Name
International Journal Of Sustainable Development And Planning
Monitoring and Prediction Functional Change of Land Uses Toward Urban Sustainability
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Urban land uses are in a dynamic state that varies over time, the city of Karbala in Iraq has experienced functional changes over the past 100 years, as the city is characterized by the presence of significant tourist and socio-economic activity represented by religious tourism, and it occur due to various reasons such as urbanization. The purpose of this study is to apply a Markov model to analyze and predict the behavior of transforming the use of land in Karbala city over time. This can include the conversion of agricultural land, or other areas into residential, commercial, industrial land uses. The process of urbanization is typically driven by population growth, economic development, based on a set of probabilities and transitions bet

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