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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 01 2019
Journal Name
Biochem. Cell. Arch
ISOLATION, IDENTIFICATION AND EVALUATION OF LACTIC ACID BACTERIA AS ANTIBACTERIAL ACTIVITY
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Five species of Lactic acid bacteriawere isolated from raw milk, yoghurt, vegetables and pickles, Lactobacillus plantarum, Lactobacillus acidophilus, Lactobacillus brevis, Lactobacillus casei and Lactobacillus bulgaricus isolates were identified by 16S rRNA gene. Evaluate of antimicrobial activity against all the bacterial strains Staphylococcus aureus, Salmonella spp., Pseudomonas fluorescens, Escherichia coli, Bacillus cereus and Bacillus subtilis. It showed that bacteriocin of Lactic acid bacteriamore effective than supernatant of lactic acid bacteria, the results showed that isolatemost efficient isolate belonging to Lactobacillus brevis, the diameter of the inhibition of the bacteriocin of Lactobacillus brevis were 27.7, 26.3 and 25.1

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Publication Date
Fri Oct 01 2021
Journal Name
International Journal Of Drug Delivery Technology
Synthesis and Preliminary Antimicrobial Activity Evaluation of New Amide Derivatives of 2-aminobenzothiazole
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Publication Date
Tue Dec 01 2020
Journal Name
Systematic Reviews In Pharmacy
Synthesis And Preliminary Antimicrobial Evaluation Of Schiff Bases Of N -Benzyl Isatin Derivatives
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Isatin (1H-indole-2, 3-dione) and its analogs are an important class of heterocyclic compounds. N-benzyl isatins and Schiff bases of isatin analogs have been reported to demonstrate a variety of biological activities. This work illustrates the synthesis of new N-benzylisatin Schiff bases and studies their biological activity. Firstly, Isatin and its analogs; 5-methoxyisatin, 5-fluoroisatin reacted with benzyl iodide to obtain N-benzylated derivatives of isatins 2 (ac). Secondly, these compounds were reacted with different amines (sulphanilamide and 4-methyl sulphonyl aniline) separately, to obtain Schiff bases compounds 3 (ac) and 4 (ac), respectively. The synthesized compounds were characterized by using FT-IR and 1HNMR spectroscopy. The s

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Publication Date
Sun Jun 05 2016
Journal Name
Baghdad Science Journal
Preparation and Spectroscopic Studies of Some Metal Ion Complexes of 2-((4-Formyl-3-Hydroxynaphthalen-2-yl) Diazenyl) Benzoic Acid
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New azo ligand 2-((4-formyl-3-hydroxynaphthalen-2-yl) diazenyl) benzoic acid (H2L) was synthesized from the reaction of 2-aminobenzoic acid and2-hydroxy-1-naphthaldehyde. Monomeric complexes of this ligand, of general formulae [MII(L)(H2O)] with (MII = Mn, Co, Ni, Cu, Zn, Pd, Cd and Hg ) were reported. The compounds were isolated and characterized in solid state by using 1H-NMR, FT-IR, UV–Vis and mass spectral studies, elemental microanalysis, metal content, magnetic moment measurements, molar conductance and chloride containing. These studies revealed tetrahedral geometries for all complexes except PdII complex is Square planar. The study of complexes formation via molar ratio of (M:L) as (1:1). Theoretical treatments of compounds in gas

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Publication Date
Thu Feb 01 2024
Journal Name
Microbial Pathogenesis
Evaluation of antibacterial, antifungal and antibiofilm activities of A. baumannii-derived tannase and gallic acid against uropathogenic microorganisms
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Publication Date
Fri Dec 01 2023
Journal Name
Iraqi Journal Of Physics
Eco-Friendly Synthesis of Ag-ZnO Nanocomposite Using Aloe-vera, Hibiscus Sabdariffa Plants and Their Antibacterial and Anti-fungi Activities
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The current study used extracts from the aloe vera (AV) plant and the hibiscus sabdariffa flower to make Ag-ZnO nanoparticles (NPs) and Ag-ZnO nanocomposites (NCs). Ag/ZnO NCs were compared to Ag NPs and ZnO NPs. They exhibited unique properties against bacteria and fungi that aren't present in either of the individual parts. The Ag-ZnO NCs from AV showed the best performance against E. coli, with an inhibition zone of up to 27 mm, compared to the other samples. The maximum absorbance peaks were observed at 431 nm and 410 nm for Ag NPs, at 374 nm and 377 nm for ZnO NPs and at 384 nm and 391 nm for Ag-ZnO NCs using AV leaf extract and hibiscus sabdariffa flower extract, respectively. Using field emission-scanning electron microscopes (FE-

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Publication Date
Sun Jun 20 2010
Journal Name
Al-qadisiya Journal For Science
Synthesis 4-phenyl -1-alkyl-1,2,4-triazoline-5-one derived from D- fructose
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The aim of the present work is the synthesis of new carbohydrate derivatives containing 1,2,4-triazole from D-fructose . To obtain these derivatives, the diacetone fructose (1 ) was chosen as the starting material, which was obtained from the reaction of anhydrous fructose with dry acetone in presence of anhydrous ferric chloride. Oxidation of ( 1) with potassium permanganate in potassium hydroxide solution gave the acid ( 2). Esterification of the acid with dimethyl sulphate gave the methyl ester (3 ). Treatment of the methyl ester (3 ) with hydrazine hydrate gave the hydrazide (4 ), which is the desired Chiron. The hydrazide (4 ) was used for the preparation of 1,2,4-triazole-5-one (6 ) derivative. These compounds was synthesized by the i

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Publication Date
Tue Feb 04 2014
Journal Name
Al-mustansiriyah
Synthesis, Spectroscopic and Biological Studies of some Metal Complexes with 2, 4-dinitro-2-amino hydrozo benzene.
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Publication Date
Thu Jul 01 2021
Journal Name
International Journal Of Drug Delivery Technology
Synthesis and Diagnosis of Some Derivatives of 1,2,4-Triazole-3-Dicarboxylic Acid and Study their Biological Activity
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Newly prepared derivatives of Heterocyclic of dicarboxylic acid include 1, 2, 4-Triazoledicarboxylic acid. Thiocarbohydrazine (TCH) reacts with aliphatic and aromatic dicarboxylic acids, and when these resulting compounds interact with compounds containing a group of carbonyl they result in Schiff base, which are very important in the industrial and medical fields and the acids used (oxalic acid, succinic, terephthalic) to prepare the triazole, then the reaction with Para-chlorobenzendihaide. and some physical properties were measured for these products. The biological activity of the prepared compounds has been studied, and it has been shown that they have different effects on the bacteria, compounds prepared with Fourier Transform Infrare

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Publication Date
Sun Oct 01 2023
Journal Name
Baghdad Science Journal
Gaussian Integer Solutions of the Diophantine Equation x^4+y^4=z^3 for x≠ y
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The investigation of determining solutions for the Diophantine equation  over the Gaussian integer ring for the specific case of  is discussed. The discussion includes various preliminary results later used to build the resolvent theory of the Diophantine equation studied. Our findings show the existence of infinitely many solutions. Since the analytical method used here is based on simple algebraic properties, it can be easily generalized to study the behavior and the conditions for the existence of solutions to other Diophantine equations, allowing a deeper understanding, even when no general solution is known.

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