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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
Fri Feb 15 2019
Journal Name
Research Journal Of Pharmaceutical, Biological And Chemical Sciences
Synthesis, Spectroscopic, Characterization and Biological Activities of Schiff Base Ligand and Metal Complexes of Some Metal (II) Salts with Anthranilic Acid
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Schiff base N,N'-Bis-(4-dimethylamino-benzylidene)-benzene-1,4-diamine has been synthesized from 4-dimethylaminobenzenaldehyde and benzene-1,4-diamine. The structure of Schiff base was obtained by (C.H.N.) microanalysis, Mass, 1HNMR, FT-IR and UV-Vis spectral methods and thermal analysis. Metal mixed ligand complexes of some metal(II) salts with Schiff base ligand and anthranilic acid were prepared in the molar ratio (1:2:2), (Metal):(SBL)2:(Anthra)2, (SBL)= Schiff base ligand, (Anthra) =anthranilic acid and Metal= Co(II), Ni(II), Cu(II), Zn(II), Cd(II) and Hg(II). The thermal behaviour (TGA) of the complexes was studied. The prepared complexes identified by using mass, thermal analysis, FT.IR and UV-Vis spectrum methods, on otherwise flame

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Publication Date
Sun Mar 05 2017
Journal Name
Baghdad Science Journal
Synthesis of Some Mixed ligands Complexes of (2-hydroxy benzaldine)-4-amino Antipyrine and 1,10-phenanthroline and Studying their antibacterial activity
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Complexes from the ligand (2-hydroxy benzaldine)-4-aminoantipyrine with some transition metal ions V(l?),Cr(lll),Fe(lll) and Co(ll) were prepared in the presence of the co-ligand 1,10-phenanthroline in alcoholic medium. These compounds were characterized by the available techniques: FT-IR ,UV-Visible ,magnetic susceptibility, Flame atomic absorption technique as well as elemental analysis and conductivity mesurments .From these spectral studies, a square pyramidal structure proposed for V(IV) complex and an octahedral geometry for Cr(III),Fe(III) and Co(II) complexes. The biological activity of the ligands and their complexes were evaluated by a gar plate diffusion technique against three human pathogenic bacterial strains: Pseudomonas ae

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Publication Date
Fri Jan 01 2010
Journal Name
Journal Of The College Of Education, Al-mustansiriya University
Synthesis and ldentification of metal complexes of 1- phenyl -3, (2'(S'phenyl amine)'l, 3, 4-thiad iazole'Z'yl) phenyl thiourea.
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Complexes of 1-phenyl-3-(2(-5-(phenyl amino)-1,3,4- thiadiazole-2-yl)phenyl) thiourea have been prepared and characteized by elemental analysis, Ff-[R, and u.v./ visible spectra moreover, determination of metal content M%o by flame atomic absorption spectroscopy, molar conductance in DMSO solution and magnetic moments (peffl. The result showed that the ligand (L) was coordinated to Mn*2, Ni*2, Ct*2,2n*2,Cd*2, and Hg*2 ions through the nitrogen atoms and sulpher atoms. From the result obtained, rhe following general formula [MLClz] has been given for the prepared complexes with an octahedral geometry around the metal ions for all complexes. where M= Mn*2, Ni*2, cu*2, zn*z, cd*z, and Hg*2 l= l-phenyl-3-(2-(5-(phenyl amino)-1, 3,

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Publication Date
Mon Jul 01 2024
Journal Name
Russian Journal Of Organic Chemistry
Synthesis and Study of the Biological Activity of New Compounds Derived from 4-(5-Phenyl-1,3,4-oxadiazole-2-yl)aniline
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Publication Date
Sun Sep 01 2013
Journal Name
Baghdad Science Journal
Synthesis and characterization of novel metal complexes of (pentulose-?-lactone-2,3-enedibenzoate barbituric acid) with some metal ions
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New (pentulose-?-lactone-2,3-enedibenzoate barbituric acid) (L) have been synthesized by reaction of (5-C-dimethyl malonyl-pentulose-?-lactone-2,3-enedibenzoate) with urea in alkaline media (sodium methoxide). (Ca+2, Co+2, Ni+2, Cu+2, Zn+2, Cd+2 and Hg+2) complexes of (pentulose-?-lactone-2,3-enedibenzoate barbituric acid) (L) have been prepared and characterized by (1H and 13CNMR), FTIR, (U.V-Vis) spectroscopy, Atomic absorption spectrophotometer (A.A.S), Molar conductivity measurements and Magnetic moment measurements, and the following general formula has been given for the prepared complexes [MLCl2(H2O)].XH2O, where M = (Ca+2, Co+2, Ni+2, Cu+2, Zn+2, Cd+2, Hg+2), X = five molecules with (Cd+2) complex, L = (pentulose-?-lactone-2,3

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Publication Date
Sun Jun 01 2014
Journal Name
Baghdad Science Journal
Anti –phytopathogenic Activities of Cladophora glomerata extract against plant fungi
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The antiphytopathogenic effects of the crude methanol extract of Cladophora glomerata (Lin.) Kützing (Cladophoraceae) which isolated from Al Rashidiya region at north of Baghdad was investigated against two type of plant fungi (Pythium altimum and Rhizoctonia solani) which causes damping off disease where isolated from covered cucumber field in Al-Alyosifia region. Hot methanol extract showed antifungal activity against the two species of fungi in different concentrations(10,25,50 mg/ml) of extract to Cladophora glomerata as percentage inhibition (51.63 ,72.8 ,83.71) and (56.18 ,77.41 ,100)comparing with Pythium altimum and Rhizoctonia solani respectively .primary detection of active compounds showed that macroalgae (Cladoph

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Publication Date
Sat Aug 01 2015
Journal Name
Journal Of Engineering
Determination of the Optimum Conditions in Evaluation of Kiwi Juice as Green Corrosion Inhibitor of Steel in Hydrochloric Acid
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The corrosion protection of low carbon steel in 2.5 M HCl solution by kiwi juice was studied at different temperatures and immersion times by weight loss technique. To study the determination of the optimum conditions from statistical design in evaluation of a corrosion inhibitor, three variables, were considered as the most dominant variables. These variables are: temperature, inhibitor concentration (extracted kiwi juice) and immersion time at static conditions.

These three variables are manipulated through the experimental work using central composite rotatable Box – Wilson Experimental Design (BWED) where second order polynomial model was proposed to correlate the studied variables with the corrosion rate o

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Publication Date
Wed Oct 16 2019
Journal Name
Journal Of Research In Medical And Dental Science
Evaluation of the Antibacterial Efficacy of Silver Nanoparticles as an Irrigant against Enterococcus faecalis In vitro Study
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Background: Successful root canal therapy depends on thorough chemo mechanical debridement of pulpal tissue, dentin debris and infective microorganisms. Objective: This study aimed to investigate the antibacterial effect of silver nanoparticles, sodium hypochlorite and chlorhexidine in reducing the bacterial infection of the root canals. Materials and Methods: The root canals of 55 single-rooted teeth were cleaned, shaped, and sterilized. All the teeth samples were inoculated with Enterococcus faecalis and incubated at 37°C for 2 weeks. Then, the teeth were divided into four groups. Group I (n=15): 100 ppm silver nanoparticles, Group II (n=15): 2.5 sodium hypochlorite, Group III (n=15): 2% chlorhexidine, IV (n=10): Normal saline as a contr

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Publication Date
Fri Jan 01 2016
Journal Name
Der Pharmacia Lettre
Synthesis, characterization and anticonvulsant evaluation of new derivatives derived from 5-methoxy-2-mercapto benzimidazole
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A new series of 5-methoxy-2-mercapto benzimidazole derivatives were synthesized by the reaction of 5-methoxy- 2-mercaptobenzimidazole with chloroacetic acid and affords 2-((5-methoxy-1H-benzo[d]imidazol-2-yl)thio) acetic acid (1),which on cyclization with acetic anhydride and pyridine gives 7- methoxybenzo[4,5]imidazo[2,1-b]thiazol- 3(2H)-one(2), which on condensation with different aryl aldehydes in the presence of anhydrous sodium acetate in glacial acetic acid, furnishes a arylidene thiazolidinone. The purity of the synthesized compounds was confirmed by melting point and TLC.The structures were established by different spectral analysis such as FTIR,1HNMR, and CHN analysis. The newly synthesized compounds (3a-d) were in vivo evaluated f

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Publication Date
Thu Jun 30 2022
Journal Name
International Journal Of Drug Delivery Technology
Synthesis of New Substituted Coumarin Derivatives containing Schiff-Base as Potential Antimicrobial and Antioxidant Agents
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By unusual method for separating two isomers of a substituted nitro-coumarin using a soxhlet extractor and in controlling temperature to get a selective nitration reaction, several new Schiff base coumarins were synthesized from nitro coumarins as starting material, which were reduced by Fe in glacial acetic acid to produce corresponding amino coumarin derivatives. Then the latter was reacted with different aromatic aldehydes to produce the desired Schiff bases derivatives. After characterization by Fourier transform infrared (FT-IR), Proton nuclear magnetic resonance (1HNMR) and Carbon-13 nuclear magnetic resonance (C-NMR), all these compounds were evaluated as potential Antimicrobial and Antioxidant Agents.

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