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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 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
Mon Apr 17 2017
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
Synthesis And Imidization Of Disuccinamic Acid As Polyvinyl Alcohol-Composite Polymer
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  Two arylenedisuccinamic acids, namely 1,4-phenylene-disuccinamic acid and 4,4'biphenyl-disuccinamic acid were prepared from the reaction of two moles of succinic anhydride with one mole of 1,4-phenylenediamine dihydrochloride and beinzidine respectively.Dehydration of arylenedisuccinamic acid in the pressence of polyvinyl alcohol (PVA) and catalytic amount of concentrated.H2SO4,gives N,N'-arylenedisuccinimidesPVAcomposite polymers. Dehydration of arylenedisuccinamic acid (without PVA) in the pressence of catalytic amount of conc. H2SO4 gives N,N'-arylenedisuccinimides. Arylenedisuccinamic acid and arylenedisuccinimides characterized by CHN-analysis,FT.IR and 1H,C13-NMR.Spectral analysis

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Publication Date
Mon Sep 16 2024
Journal Name
Plant Protection
In vitro investigation of phytochemical, antioxidant and antimicrobial activities of Harpagophytum procumbens seeds extracts
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Medicinal plants contain bioactive substances that are highly bioavailable in extracts or pure molecules, making them promising for therapeutic applications and precursors for chemo-pharmaceutical semi-synthesis. Harpagophytum procumbens (Devil’s Claw) is widely recognized as one of the most potent therapeutic herbs. This study aimed to extract seeds from H. procumbens using two types of solvents and to assess both qualitative and quantitative aspects of the extracts. The two extracts were evaluated for antibacterial and anti-biofilm activities using agar well diffusion assays against four bacterial isolates and two yeast isolates. Qualitative analysis identified the presence of alkaloids, flavonoids, tannins, saponins, and terpen

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Publication Date
Mon Sep 16 2024
Journal Name
Plant Protection
In vitro investigation of phytochemical, antioxidant and antimicrobial activities of Harpagophytum procumbens seeds extracts
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Medicinal plants contain bioactive substances that are highly bioavailable in extracts or pure molecules, making them promising for therapeutic applications and precursors for chemo-pharmaceutical semi-synthesis. Harpagophytum procumbens (Devil’s Claw) is widely recognized as one of the most potent therapeutic herbs. This study aimed to extract seeds from H. procumbens using two types of solvents and to assess both qualitative and quantitative aspects of the extracts. The two extracts were evaluated for antibacterial and anti-biofilm activities using agar well diffusion assays against four bacterial isolates and two yeast isolates. Qualitative analysis identified the presence of alkaloids, flavonoids, tannins, saponins, and terpen

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Publication Date
Mon Jan 01 2024
Journal Name
Russian Journal Of Organic Chemistry
Synthesis and Biological Activity of Some New 1,3,4-Oxadiazoles Derived from Carboxylic Acids
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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
Mon Jun 04 2018
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Synthesis and antimicrobial evaluation with DFT study for new thiazole derivatives
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Two compounds,[2-amino-4-(4-nitro phenyl) 1,3-thiazole],(4) and [2-amino-4-(4-bromo phenyl) 1,3-thiazole],(5), were synthesized by refluxing thiourea (1) with each of  para-ntiro and para-bomophanacyl bromides(2) and (3) respectively, in absolute methanol. Then, by reaction of [5] with 3,5-dinitrobenzoyl chloride in dimethylformamide (DMF) yielded  (6) .On the other hand, reaction of (4) with chloroacetyl chloride in dry benzene afforded (7), which is  upon treatment with thiourea in absolute methanol, af

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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
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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