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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
Cytotoxic Activities, Determining Toxin, and Molecular Docking of Ovary Pufferfish (Tetraodon leiurus) in Singkarak Lake as Cancer Chemoprevention Candidate
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The primary toxin class discovered in freshwater pufferfish is a category of neurotoxins called PSTs (Paralytic shellfish toxins) and pufferfish toxin has been observed to have biological, biochemical, and cytotoxic effects on cancer cell lines. Therefore, it is crucial to determine the cytotoxic activity, toxins present in the ovary of T. leiurus, and interaction between ligand (toxin compound) and receptors test. This study used the MTT method in the T47D cell lines, liquid chromatograph-tandem mass spectrometry (LC-MS/MS), and analysis of the molecular interaction using molecular docking. The ovary of T. leiurus had cytotoxicity on the T47D cell, having an IC50 value of 229.535 μg/ml, and generated a chroma

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Publication Date
Fri Aug 18 2023
Journal Name
Pharmacia
Synthesis, characterization, and antimicrobial evaluation of new Schiff bases derived from vanillic acid conjugated to heterocyclic 4H-1,2,4-triazole-3-thiol
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A multistep synthesis was established for the preparation of a new vanillic acid-1, 2, 4-1triazole-3-thiol conjugate (4). Finally, several aromatized aldehydes reacted with compound (4) to produce Schiff bases derivatives (5–11). The purpose of this research is to prepare new vanillic acid derivatives with 1, 2, 4-triazole-3-thiol heterocyclic ring structures and to evaluate their antimicrobial activity in a preliminary assessment. Fourier-transform infrared (FT-IR) and proton nuclear magnetic resonance spectroscopy (1H-NMR) were used to verify the structures of the newly synthesized compounds. all the final synthesized compounds (

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Publication Date
Wed Oct 04 2023
Journal Name
History Of Medicine
Theoretical Biological Activities and Docking studies of new amino-acids Derivatives of Oseltamivir for The Treatment of Coronavirus Disease 2019
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Antiviral medications may be the best choices for COVID-19 treatment until particular therapeutic treatments become available. Tamiflu (oseltamivir) is a neuraminidase inhibitor licensed for the management and defense against influenza types A and B. Oseltamivir-based medication combinations are currently being used to treat COVID-19 patients who also have the new coronavirus 1 SARS-CoV-2. 1 Oseltamivir administration was related with a less time spent in the hospital, quicker recovery 1 and discharge, and a decreased mortality rate. Docking is a modern computational method for identifying a hit molecule by assessing the binding ability of molecular medicines within the binding target pocket. In this work, we chose 21 ligand compounds that

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Publication Date
Mon Mar 18 2019
Journal Name
Baghdad Science Journal
Enhancement of hydrothermally Co <sub>3</sub> O <sub>4</sub> thin films as H <sub>2</sub> S gas sensor by loading yttrium element
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The gas sensing properties of Co3O4and Co3O4:Y nano structures were investigated. The films were synthesized using the hydrothermal method on a seeded layer. The XRD, SEM analysis and gas sensing properties were investigated for Co3O4and Co3O4:Y thin films. XRD analysis shows that all films are polycrystalline in nature, having a cubic structure, and the crystallite size is (11.7)nm for cobalt oxide and (9.3)nm for the Co3O4:10%Y. The SEM analysis of thin films obviously indicates that Co3O4possesses a nanosphere-like structure and a flower-like structure for Co3O4:Y.The sensitivity, response time and recovery time to a H2S reducing gas were tested at different operating

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Publication Date
Mon Oct 07 2019
Journal Name
Journal Of Global Pharma Technology
Contribution of Equilibrium Variables with the High Spike Accuracy of the Position Diagonal Center (4) in the National Volleyball Team Players
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What is important about this study is whether there is a relationship between the ability to balance and beating overwhelming for the Iraqi national team volleyball? The study aims to identify the percentage of the equilibrium contribution and its variables with the accuracy of the skill of beating the high spike Diagonal center (4) in the players. In the national volleyball team season (2016-2017), the researchers used the descriptive approach in the style of associative relationships to suit the problem of research. The research community included all the players specialized in the high beating of the Iraqi national team applicants in the ball The researchers concluded that the equilibrium variables contributed accurately and quickly to t

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Publication Date
Thu Jan 01 2009
Journal Name
Journal Of Global Pharma Technology
Contribution of Equilibrium Variables with the High Spike Accuracy of the Position Diagonal Center (4) in the National Volleyball Team Players
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Publication Date
Wed Sep 14 2016
Journal Name
Journal Of Baghdad College Of Dentistry
The Effect of Thymosin Beta 4 on Developing Dental Tissue (Experimental Study on Rats)
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Background: Odontogenisis is a complex process controlled by dynamic and reciprocal interactions that regulated by various molecules. Thymosin β4 is a small bioactive peptide with wide spectrum biological effects on much cell types. The present study was designed to highlight the effect of synthetic exogenous Tβ4 on developing dental tissue of the upper central teeth of rats, by histological examination and immunohistochemical evaluation of TGFβ1. Materials and method: Thirty six Albino Wister pregnant rat 18control group received intraperitoneal injection of normal saline and the others are experimental group received 50µg/300µl of Tβ4 injection. The animals were sacrificed at periods 16th and 18th day I.U.L and one day p

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Publication Date
Thu Mar 25 2021
Journal Name
International Journal Of Drug Delivery Technology
Spectrophotometric Estimation of the Lansoprazole by Oxidative Coupling Reaction with 2, 4-Dinitrophenyl Hydrazine
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ABSTRACT A simple, accurate, sensitive, and low-cost technique was advanced to measure the optical spectrum to the determination of lansoprazole in pure form and dosage forms. The method relies on the oxidation of the reagent 2,4-dinitrophenylhydrazine (2,4-DNPHz) with potassium periodate (KIO4) and coupling with the Lansoprazole (LPZ) in the alkaline medium to form a stable with reddish-brown colored dye with a maximum greatest absorption at 484.5 nm. The reaction is carefully completed when optimizing the variable affecting it. The concentration range from 1-30 μg/mL obegs Beer’s law and the molar absorptivity value of (13260.132) L/mol.cm. Detection limit was (0.1266 μg/mL) and Sandell’s sensitivity value ( 0.0278) μg/cm2. The met

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Publication Date
Sun Sep 22 2019
Journal Name
Baghdad Science Journal
Synthesis and Characterization of New Selenonitrone Derivative and Its Effect on Breast Cancer Cell Line Viability in Vitro
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          New nitrone and selenonitrone compounds were synthesized. The condensation method between N-(2-hydroxyethyl) hydroxylamine and substituted carbonyl compounds such as [benzil, 4, 4́-dichlorobenzil and  2,2́ -dinitrobenzil] afforded a variety of new nitrone compounds while the condensation between N-benzylhydroxylamine and substituted selenocarbonyl compounds such as [di(4-fluorobenzoyl) diselenide and (4-chlorobenzoyl selenonitrile] obtained selenonitrone compounds. The condensation of N-4-chlorophenylhydroxylamine with dibenzoyl diselenide obtained another type of selenonitrone compounds. The structures of the synthesized compounds were assigned based on spectroscopic data (FT-IR,

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Publication Date
Fri Feb 15 2019
Journal Name
Route Educational & Social Science Journal
The effect of the 4-H model on self-regulated learning and life skills for female chemistry students in the second intermediate year
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