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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
Mon Jul 01 2024
Journal Name
International Journal Of Engineering In Computer Science
Human biometric identification: Application and evaluation
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Publication Date
Mon Aug 26 2019
Journal Name
Global Proceedings Repository American Research Foundation
Preparation, Spectra and Biological Properties of Transition Metals ((III) and (II) Mixed - Ligand Complexes with 5-Chlorosalicylic Acid and L-Valine
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Mixed ligand metal complexes of CrIII, FeIII,II, NiII and CuII have been synthesized using 5-chlorosalicylic acid (5-CSA) as a primary ligand and L-Valine (L-Val) as secondary ligand. The metal complexes have been characterized by elemental analysis, electrical conductance, magnetic susceptibility measurements and spectral studies. The electrical conductance studies of the complexes indicate their electrolytic nature. Magnetic susceptibility measurements revealed paramagnetic nature of the all complexes. Bonding of the metal ion through –OHand –COOgroups of bidentate to the 5-chlorosalicylic acid and through –NH2 and –COOgroups of bidentate to the L-valine by FT-IR studies . The agar diffusion method has been used to study the antib

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Publication Date
Fri Jan 11 2019
Journal Name
Global Proceedings Repository American Research Foundation
Preparation, Spectra and Biological Properties of Transition Metals ((III) and (II) Mixed - Ligand Complexes with 5-Chlorosalicylic Acid and L-Valine
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Mixed ligand metal complexes of CrIII, FeIII,II, NiII and CuII have been synthesized using 5-chlorosalicylic acid (5-CSA) as a primary ligand and L-Valine (L-Val) as secondary ligand. The metal complexes have been characterized by elemental analysis, electrical conductance, magnetic susceptibility measurements and spectral studies. The electrical conductance studies of the complexes indicate their electrolytic nature. Magnetic susceptibility measurements revealed paramagnetic nature of the all complexes. Bonding

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Publication Date
Sun Mar 01 2020
Journal Name
Journal Of Engineering
Performance Evaluation of Trickling Filter and Extended Aeration of Wastewater Treatment Plants
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In recent decades, there has been increasing interest in wastewater treatment because of its direct impact on the environment and public health. Over time, other forms of treatment have been developed and modified, including extended aeration. This process is included in the suspended growth system. In this paper, a comparative study was conducted between the efficiency of the extended aeration plant and that of the trickling filter plant in removal of BOD and COD.  The method of comparison was done by knowing the value of the pollutant before and after the treatment and then extract the removal ratio of each pollutant within each plant. The results showed that the percentage of removal of BOD in the trickling filte

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Publication Date
Wed Mar 10 2021
Journal Name
Baghdad Science Journal
Evaluation of Hemolysis Activity of Zerumbone on RBCs and Brine Shrimp Toxicity
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Zerumbone is a well-known compound having anti-cancer, anti-ulcer, anti-inflammatory and anti-hyperglycemic effects. During its use for the disease treatment, the membrane of erythrocyte can be affected by consumption of this bioactive compound. The current study was the first report of investigation of the hemolytic activities on human erythrocytes and cytotoxic profile of zerumbone. The toxicity of zerumbone on human erythrocytes was determined by in vitro hemolytic assay. Brine shrimp lethality assay was used to evaluate the cytotoxic effect of zerumbone at concentrations 10, 100 and 1000 μg/mL. The human erythrocyte test showed no significant toxicity at low concentrations, whereas hemolytic effect was amplified up to 17.5

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Publication Date
Wed Mar 29 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Preparation and Evaluation of Oral Disintegrating Tablets of Ketoprofen by Dirct Compression
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Ketoprofen is a non-steroidal anti-inflammatory (NSAID) drug with analgesic, anti-inflammatory, and antipyretic effects. It is widely used in the treatment of inflammation and pain associated with rheumatic disorders such as rheumatoid arthritis, osteoarthritis, and in soft tissue injury. The purpose of this study was to prepare an  oral disintegrating tablets of ketoprofen by simple method. The tablets were prepared by direct compression method and different ratios of various subliming agents or superdisintegrants were incorporated. Then these tablets were evaluated for hardness, friability, weight variation, water absorption ratio, disintegrating time and dissolution time. The results showed that Formula F11 batch had short disint

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Publication Date
Wed Mar 10 2021
Journal Name
Baghdad Science Journal
Evaluation of Hemolysis Activity of Zerumbone on RBCs and Brine Shrimp Toxicity
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Zerumbone is a well-known compound having anti-cancer, anti-ulcer, anti-inflammatory and anti-hyperglycemic effects. During its use for the disease treatment, the membrane of erythrocyte can be affected by consumption of this bioactive compound. The current study was the first report of investigation of the hemolytic activities on human erythrocytes and cytotoxic profile of zerumbone. The toxicity of zerumbone on human erythrocytes was determined by in vitro hemolytic assay. Brine shrimp lethality assay was used to evaluate the cytotoxic effect of zerumbone at concentrations 10, 100 and 1000 μg/mL. The human erythrocyte test showed no significant toxicity at low concentrations, whereas hemolytic effect was amplified up to 17.5 % at

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Publication Date
Thu Sep 13 2018
Journal Name
Baghdad Science Journal
Synthesis and Fabrication of In2O3: CdO Nanoparticles for NO2 Gas Sensor
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The physical and morphological characteristics of porous silicon (PS) synthesized via gas sensor was assessed by electrochemical etching for a Si wafer in diluted HF acid in water (1:4) at different etching times and different currents. The morphology for PS wafers by AFM show that the average pore diameter varies from 48.63 to 72.54 nm with increasing etching time from 5 to 15min and from 72.54 to 51.37nm with increasing current from 10 to 30 mA. From the study, it was found that the gas sensitivity of In2O3: CdO semiconductor, against NO2 gas, directly correlated to the nanoparticles size, and its sensitivity increases with increasing operating temperature.

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Publication Date
Sun Dec 06 2015
Journal Name
Baghdad Science Journal
Synthesis, Characterization and Study the Biological Activity of New Morpholine Derivative
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A new series of morpholine derivative were prepared by reacting the morpholine with ethyl chloro acetate in the presence triethylamine as an catalyst and benzene as a solvent gave the ethyl morpholin-4-ylacetate reaction with hydrazine hydrate and ethanol as a solvent gave the 2-(morpholin-4-yl)acetohydrazide gave series of Schiff base were prepared by reacting 2-(morpholin-4- yl)acetohydrazide with different aromatic aldehydes and ketons . The new series of (3-9 )were synthesis by reaction of Schiff base (10-14) with chloroacetyl chloride, triethyl amine as an catalyst and 1,4dioxane as a solvent .The chemical structures of the synthesis compound were identified by spectral methods their [ IR ,1H-NMR and 13C-NMR ].The synthesised compoun

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Publication Date
Mon Aug 01 2022
Journal Name
Baghdad Science Journal
Recycling of Chicken Egg Shells into Nanopowder: Synthesis, and its Properties
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Increase in unconventional resources of calcium (Ca+2) for fowls, aquaculture and native animals was improved. This work was planned to define the most polymorph of calcium carbonate (CaCO3) that take place in the two types of chicken eggshells (local and imported type). In this research, the comparative analysis of calcium carbonate (CaCO3) content was approved for nominated eggshells of native strain and imported chicken via Field Emission Scanning Electron Microscope (FESEM), Transmission Electron Microscope (TEM), Fourier-Transform Infrared Spectroscopy (FTIR) and Powder X-Ray Diffraction (PXRD) analysis. The results demonstrate that native and imported chicken eggshells comprise calcite morph that ha

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