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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
Sun Sep 01 2013
Journal Name
Baghdad Science Journal
In Vitro Study of MefenamateStarch as Drug Delivery System
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Mefenamic acid was esterified with starchwith[1:1] Molar ratio, as drug substituted with natural polymer, to prolongthe period of hydrolysis of drug polymer with other advantages. The new prodrug starch was characterized by FT-IR and UV-Visible and 1H-NMR spectroscopies. The physical properties were studied and controlled drug release was studied in different pH values at 37oC. The stability of drug was carried out by measuring the absorbance of mefenamic starch which hydrolyzed in HCl solution of pH 1.1 (artificial gastric fluid) and phosphate buffer of pH 7.4 (simulating intestinal fluid SIF) at 37oC for several days. The thermal analysis such as DSC was studied.

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Publication Date
Sun Jan 01 2017
Journal Name
Disease Markers
Genotyping of<i> IL-4</i> −590 (C&gt;T) Gene in Iraqi Asthma Patients
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This study is the first investigation in Iraq dealing with genotyping of IL-4 −590 (C>T) gene, especially in Iraqi patients with asthma. We studied forty-eight blood samples collected from patients with asthma and compared with age-matched 25 healthy individuals as controls. The polymorphism results of IL-4 −590 (C>T) gene by using amplification refractory mutation system (ARMS-PCR) showed the presence of C and T alleles and three genotypes (CC, CT, and TT). Interestingly the frequency of C allele and CC genotype was higher in patients with asthma in comparison with the same allele and geno

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Publication Date
Wed Dec 01 2021
Journal Name
Baghdad Science Journal
A complete (48, 4)-arc in the Projective Plane Over the Field of Order Seventeen
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            The article describes a certain computation method of -arcs to construct the number of distinct -arcs in  for . In this method, a new approach employed to compute the number of -arcs and the number of distinct arcs respectively. This approach is based on choosing the number of inequivalent classes } of -secant distributions that is the number of 4-secant, 3-secant, 2-secant, 1-secant and 0-secant in each process. The maximum size of -arc that has been constructed by this method is . The new method is a new tool to deal with the programming difficulties that sometimes may lead to programming problems represented by the increasing number of arcs. It is essential to reduce the established number of -arcs in each cons

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Publication Date
Mon Nov 23 2015
Journal Name
Sultan Qaboos University Medical Journal
Association of Higher Defensin β-4 Genomic Copy Numbers with Behçet’s Disease in Iraqi Patients
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Publication Date
Wed Mar 01 2023
Journal Name
Al-khwarizmi Engineering Journal
Expired Colxacillin, Amoxicillin, and Ceflaxin Drugs as Inhibitors for Low Carbon Steel Corrosion in Sodium Chloride
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The ability to inhibit corrosion of low carbon steel in a salt solution (3.5%NaCl) has been checked with three real expired drugs (Cloxacillin, Amoxicillin, Ceflaxin) with variable concentrations (0, 250, 500, 750) mg/L were examined in the weight loss. The inhibition efficiency of the Cloxacillin 750 mg/L showed the highest value (82.8125 %) and the best inhibitor of the rest of the antibiotics. The different concentrations of Cloxacillin drug (0, 250, 500, 750) mg/L and temperature (25, 35, 45, 55) oC were studied as variables with potentiodynamic polarization, Scanning Electron Microscopy (SEM) for surface morphology and electrochemical impedance spectroscopy (EIS) depending on current values and the resistance of charge to

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Publication Date
Fri Jun 09 2023
Journal Name
Journal Of Research In Medical And Dental Science
Evaluation of the Anti-inflammatory of Leucaena leucocephala extracts in Experimental Rats.
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A lot of previous studies are concerned with the evaluation of the anti-inflammatory activity of medicinal plants because it considered cheap and are believed to possess minimal side effects. Leucaena leucocephala didn’t evaluate globally for its anti-inflammatory effect yet though some of it’s already separated and identified secondary metabolites were studied and proved to exert many pharmacological activities besides their effect on lowering the pro-inflammatory cytokines like TNF-α and IL-6. So, there was an interest to evaluate the biological effect of Leucaena leucocephala as a novel anti-inflammatory agent was the first motivation to start an in vivo study using a rat population. The N-butanol and ethyl acetate extracts were cho

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Publication Date
Wed Nov 01 2023
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Synthesis, Characterization, and Preliminary Evaluation of Antimicrobial activity of Imines derived from Vanillic Acid Conjugated to Heterocyclic
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The purpose of this research is to prepare new vanillic acid derivatives with 1,2,4-triazole-3-thiol heterocyclic ring and evaluate their antimicrobial activity in a preliminary assessment. A multistep synthesis was established for the preparation of new vanillic acid-triazole conjugates. The intermediate of 4-(4-amino-5-mercapto-4H-1,2,4-triazol-3-yl)-2-methoxyphenol (4) reacts with different heterocyclic aldehydes (thiophene-2-carboxaldehyde, pyrrole-2-carboxaldehyde, thiophene-3-carboxaldehyde, and furfural ) in ethanol containing few drops of acetic acid yielded the corresponding 4-(4-(substituted amino)-5-mercapto-4H-1,2,4-1triazol-3-yl)-2-methoxy phenol derivatives (

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Publication Date
Wed Nov 01 2023
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Synthesis, Characterization, and Preliminary Evaluation of Antimicrobial activity of Imines derived from Vanillic Acid Conjugated to Heterocyclic
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The purpose of this research is to prepare new vanillic acid derivatives with 1,2,4-triazole-3-thiol heterocyclic ring and evaluate their antimicrobial activity in a preliminary assessment. A multistep synthesis was established for the preparation of new vanillic acid-triazole conjugates. The intermediate of 4-(4-amino-5-mercapto-4H-1,2,4-triazol-3-yl)-2-methoxyphenol (4) reacts with different heterocyclic aldehydes (thiophene-2-carboxaldehyde, pyrrole-2-carboxaldehyde, thiophene-3-carboxaldehyde, and furfural ) in ethanol containing few drops of acetic acid yielded the corresponding 4-(4-(substituted amino)-5-mercapto-4H-1,2,4-1triazol-3-yl)-2-methoxy phenol derivatives (5-8). These compounds were characterized spectroscopically by

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Publication Date
Sun Jun 01 2014
Journal Name
Journal Of Natural Science Research
Sialic Acid Is A Novel Biochemical Marker In Sera Of Iraqi Endometriotic Patients
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ABSTRACT : Alzheimer’s disease (AD) is one of the most common inflammatory neurodegenerative diseases linked with dementia, it is characterized by the deposition of amyloid beta-peptide (Ab) in the brain. The present study aims to innovate a biochemical relationship between AD and interleukin 38 (IL-38) as an anti-inflammatory cytokine, expose novel mechanisms and concepts regarding other biochemical parameters studied previously or recently in AD patients and also examine the biochemical action of memantine (10 mg daily) on AD patients. Sixty (60) diagnosed AD patients participated in the present study and classified into four (4) groups: G3 were composed of (15) newly diagnosed males (52-78) years / without treatment, G4 composed of (15

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Publication Date
Sun Mar 02 2014
Journal Name
Baghdad Science Journal
Exploiting the diazotization reaction of 4- minoacetophenone for Methyldopa determination.
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Based on the diazotization reaction of 4-aminoacetophenone with sodium nitrite in acid medium to form diazonium salt, which was coupled with Methyldopa to form a violet reddish soluble azo dye with maximum absorbance at 560 nm,a batch procedure had been developed for the estamination of Methyldopa. Under optimum experimental parameters affecting on the development and stability of the colored product, Beer´s law obeyed in the range (0.5-45) ?g.ml-1 with a correlation coefficient (0.9979).The proposed method was successfully applied to the determination of Methyldopa in either pure form and in commercial brands of pharmaceuticals, no interference was observed from common excipients in the formulations. The analytical results obtained by app

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