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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 Dec 18 2017
Journal Name
Al-khwarizmi Engineering Journal
Prediction of Surface Roughness and Material Removal Rate in Electrochemical Machining Using Taguchi Method
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Electrochemical machining is one of the widely used non-conventional machining processes to machine complex and difficult shapes for electrically conducting materials, such as super alloys, Ti-alloys, alloy steel, tool steel and stainless steel.  Use of optimal ECM process conditions can significantly reduce the ECM operating, tooling, and maintenance cost and can produce components with higher accuracy. This paper studies the effect of process parameters on surface roughness (Ra) and material removal rate (MRR), and the optimization of process conditions in ECM. Experiments were conducted based on Taguchi’s L9 orthogonal array (OA) with three process parameters viz. current, electrolyte concentration, and inter-electrode gap. Sig

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Publication Date
Sun Sep 07 2008
Journal Name
Baghdad Science Journal
Corrosion Inhibition of Al-Si-Cu Alloy in the Basic Media by UsingSix Inhibitors at Four Temperatures
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The research involved attempt to inhibit the corrosion of Al-Si-Cu alloy in 2.5x10-3 mol.dm-3 NaOH solution (pH=11.4) by addition of six different inhibitors with three concentrations (1x10-3, 1x10-2, and 0.1 mol.dm-3). These inhibitors include three organic materials (sodium acetate, sodium benzoate, and sodium oxalate) and three inorganic materials (sodium chromate, disodium phosphate, and sodium sulphate). The data that concerning polarization behaviour are calculates which include the corrosion potential (Ecorr) and current density (icorr), cathodic and anodic Tafel slopes (bc & ba), and polarization resistance (Rp). Protection efficiency (P%) and activation energy (Ea) values were calculated for inhibition by the six inhibitors. The

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Publication Date
Thu Jun 08 2017
Journal Name
International Journal Of Applied Chemistry
Synthesis and characterization of some New Oxazepine Compounds Containing 1,3,4-Thiadiazole Ring Derived form D-Erythroascorbic Acid
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This search include the synthesis of some new 1,3-oxazepine derivatives have been prepared, starting from reaction of L-ascorbic acid with dry acetone in presence of dry hydrogen chloride afforded the acetal (I). Treatment of the latter with p-nitrobenzoyl chloride in dry pyridine yielded the ester (II) which was dissolved in (65%) acetic acid in absolute ethanol yielded the glycol (III). The reaction of the glycol (III) with sodium periodate in distilled water at room temperature produced the aldehyde (IV). The compound (V) [2-amino-5-mercapato-1,3,4-thiadiazole] was prepared through the reaction of thiosemicarbazide with carbon disulphide (CS2) in entity of anhydrous (Na2CO3) in (abs. ethanol ). Compound (VI) [2-(5-mercapto-1,3,4-thiadiaz

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Publication Date
Tue Dec 01 2020
Journal Name
International Journal Of Pharmaceutical Research
Synthesis of Some New Schiff Bases Starting from 2,2 Dimorpholinyl Acetic Acid and Evaluating the Biological activity
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n this study new derivatives of Schiff bases (5-10) were synthesized from the new starting material 1 . Which has been synthesized by the reaction of (1 mol.) of dichloroacetic acid with two moles of morpholine, in the presence of potassium hydroxide, Ester derivatives 2 and 3 were synthesized by the reaction of 1 with methanol or ethanol respectively in the presence of sulphuric acid as catalyst . Compound 2 was also prepared from dimethylsulphate with high yield , 2 and 3 was used to synthesized 2,2-dimorpholinylacetohydrazide 4 via reaction with NH2NH2.H2O 80% .Imines (5-10) were synthesized via the reaction of 4 with appropriate aromatic aldehydes in the presence of G.A.A as a catalyst . Derivatives compounds (1-10) were identifie

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Publication Date
Mon Dec 31 2018
Journal Name
Journal Of The Faculty Of Medicine Baghdad
Dyslipidemia and CA15-3 serum level in Iraqi Women with Breast Tumor: A Comparative Study
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Publication Date
Mon Apr 01 2024
Journal Name
Indonesian Journal Of Chemistry
Preparation, Characterization, and Biological Activity of La(III), Nd(III), Er(III), Gd(III), and Dy(III) Complexes with Schiff Base Resulted from Reaction of 4-Antipyrinecarboxaldehyde and 2-Aminobenzothiazole
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The research includes the preparation of several complexes of the internal transition elements lanthanide (Ln = La, Nd, Er, Gd, and Dy) containing the 4f shell, with Schiff bases resulting from condensation reactions between 4-antipyrinecarboxaldehyde and 2-aminobenzothiazoles. Schiff's base was identified using FTIR spectra, UV-vis spectroscopy, elemental microanalysis CHNSO, nuclear magnetic resonance, mass spectrometry, and TGA thermal analysis. The complexes were studied and identified with elemental microanalysis CHNSO, FTIR spectroscopy, UV-vis spectroscopy, TGA thermal analysis, conductivity measurement, and magnetic sensitivity. The result showed that these complexes were classified as homogeneous bidentate complexes with th

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Publication Date
Wed Feb 22 2023
Journal Name
Iraqi Journal Of Science
Revealed of A novel Allele in Wasit – Iraqi Population
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The developments in forensic DNA technology have led us to perform this study in Iraqi population as reference database of autosomal Short Tandem Repeat (aSTR) DNA markers . A total of 120 unrelated individuals from Wasit province were analyzed at 15 STR DNA markers. Allele frequencies of DNA typing loci included in the AmpFlSTR1 IdentifilerTM PCR Amplification Kit panel from Applied Biosystems (D3S1358, vWA, FGA, D8S1179, D21S11, D18S51, D5S818, D13S317, D7S820, TH01, TPOX, CSF1PO, D19S433, D2S1338, D16S539) and several forensic efficiency statistical parameters were estimated from all the sample. the combined Matching Probability (CMP) using the 15 STR genetic loci in Iraqi population was estimated at 1 in 2.08286E-18 and the Combined

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Publication Date
Sun Jan 01 2023
Journal Name
The Egyptian Journal Of Hospital Medicine
High Tumor Levels of Ki-67, VEGF and Endostatin Are Associated with Progression of Breast Cancer in Iraqi Women
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Publication Date
Tue Jan 03 2023
Journal Name
The Egyptian Journal Of Hospital Medicine
High Tumor Levels of Ki-67, VEGF and Endostatin Are Associated with Progression of Breast Cancer in Iraqi Women
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Background: Breast cancer (BC) is the most widespread cancer among women worldwide. Its incidence and mortality rates have risen in the previous three decades as a result of changes in risk factor profiles, improved cancer registry, and cancer detection. Objective: The study's goals were to establish if Ki-67 could be used as a potential marker in serum of cancer disease patients as well as their interaction with vascular endothelial growth factor (VEGF) and ES in various stages of breast cancer to assess their function in the progression of BC. Materials and Methods: The levels of Ki-67, VEGF and endostatin (ES) in serum were assessed by commercial enzyme linked immunosorbent assay (ELISA) kits in 60 women diagnosed with breast cancer

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Publication Date
Sun Sep 06 2009
Journal Name
Baghdad Science Journal
Regeneration and Cormels Production of White Prosperity and Priscilla Gladiolus Varities In Vitro
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Plant regeneration and cormel production was carried out from callus cultures initiated from White Prosperity and Priscilla Gladiolus Varities. It is aimed to produce plants and cormels in vitro all year round. The study included many experiments, these were the effect of Naphthalene acetic acid (NAA) and Kinetin (Kin) interaction on callus initiation, effect of Benzyl adenine (BA) on shoot regeneration from callus culture, effect of NAA on rooting after 30, 40 and 50 days in culture. The role of the type of agricultural medium (Peat moss or river sand and their mixture on plantlets survival after weaning was studied. Results showed that the interaction between NAA and Kin induced callus on axillary bud explants. Callus was best ini

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