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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
Wed Sep 02 2020
Journal Name
International Journal Of Drug Delivery Technology
Synthesis of Levofloxacin Derivatives with some Amines and their Complexes with Copper(II) Salts and Evaluation of their Biological Activity
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Levofloxacin belongs to the fluoroquinolone family; it is a potent broad-spectrum bactericidal agent. The pharmacophore required for significant antibacterial activity is the C-3 carboxylic acid group and the 4-pyridine ring with the C-4 carbonyl group, into which binding to the DNA bases occur. In this work, we tried to show that by masking the carboxyl group through amide formation using certain amines to form levofloxacin carboxamides, an interesting activity is kept. Levofloxacin carboxamides on the C-3 group were prepared, followed by the formation of their copper complexes. The target compounds were characterized by FT-IR, elemental analysis. The antimicrobial activity of the target compounds was evaluated and showed satisfactory resu

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Publication Date
Tue Jan 01 2013
Journal Name
Journal Of Babylon University
Synthesis and Identification of Pyromellitamic diacids and Pyromellitdiimides derivatives.
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New derivatives of pyromellitamic diacids and pyromellitdiimides have been prepared by the reaction of one mole of pyromellitic dianhydride with two moles of aromatic amines, these derivatives were characterized by elemental analysis, FT-IR and melting point.

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Publication Date
Fri Dec 31 2021
Journal Name
Teikyo Medical Journal
Evaluation of Serum Angiogenic and Anti-angiogenic Markers in Pregnant Women with Placenta Accreta
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Over the last 40 years, rate of cesarean delivery has risen from less than10% to over 30% around the world, and almost simultaneously a 10-foldraise in the incidence of placenta accrete spectrum. Fine coordinationamong vascular endothelial growth factor, soluble fms-like tyrosine kinase1 and placental growth factor is important for normal placentaldevelopment and trophoblast invasion. To measure and compare the levelsof circulating vascular endothelial growth factor, placental growth factorand soluble fms-like tyrosine kinase 1 in pregnant women with placentaaccreta to a control group. A case control study which involved one hundredpregnant females were recruited from the Obstetric ward in BaghdadTeaching Hospital who were pregnant with 28

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Publication Date
Mon Sep 25 2017
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
Synthesis,Charaterization and Biological Activity Studies of Some Transtion and Non transition Metalcomplexes with(4 – Dithiocarbamato-N-(5- methylisoxazole-3-yle)- ion-ligand)
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This work involves the preparation of the ligand [KL] :-                    Â­Â­Â­Â­Â­Â­

K[4-(N-(5-methylisoxazol-3-yl) sulfamyl) phenylcarbamodithioate] from the reaction of sulfamethoxazole  with Carbon disulfide  in the presence of  potassium hydroxide under reflux (4 hours) using methanol as asolvent. The prepared ligand was characterized using FT-IR, UV-Vis, 1H,13C–NMR spectroscopy, molar conductivity and melting point,  Complexes for the above ligand [KL] with some bivalent transition and non-transition metals (Mn +2, Co+2  , Ni+2  ,

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Publication Date
Fri Feb 01 2019
Journal Name
Journal Of Pharmaceutical Sciences And Research
Synthesis of some Schiff base metal complexes involving trimethoprim and 2'-amino-4-chlorobenzophenone: Spectral, thermal, DNA Cleavage antimicrobial,antifungal and Cytotoxic activity studies
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In study of effective bioactive compounds, we have synthesized the Co((ІІ), Mn(ІІ), Fe(ІІ), Cu(ІІ), Ni(ІІ), and Zn(ІІ) complexes of the Schiff base derived from trimethoprim and2'-amino-4-chlorobenzophenone and characterized by spectroscopic (NMR, IR, Mass, UV–vis,), analytical, TGA studies and magnetic data .The solution electronic spectral study suggests the stoichiometry of the synthesized complexes and Elemental analysis detected the square planer and octahedral geometry of the compounds. The prepared metal complexes presented promoted efficiency versus the screened bacterial (Escherichia Coli and Staphylococcus aureus) antibacterial efficacy against (Staphylococcus aureus, Salmonella spp., E. coli, Vibrio spp., Pseud

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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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Publication Date
Fri Jan 01 2010
Journal Name
Journal Of The College Of Languages (jcl)
§ 4. МЕЖДОМЕТИЯ В ТВОРЧЕСТВЕ В.М.ШУКШИНА И ИХ ИССЛЕДОВАНИЕ.
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Творчество В.М. Шукшина богато междометиями, что замечали многие литературные критики и исследователи языка писателя. В.М.Шукшина считают одним из новаторов в особом использовании разговорной речи как литературного приема. Эту особенность своих произведений комментировал и сам писатель.

Разговорная речь – это разновидность литературного языка, реализующаяся преимущественно в устной форме в ситу

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Publication Date
Tue Jun 16 2020
Journal Name
Baghdad Science Journal
Qualitative and Quantitative Evaluation of Active Constituents in Callus of Lavandula angustifolia plant in Vitro
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This study was conducted to describe a protocol for the callus establishing culture of Lavandula angustifolia plant and estimating their content of volatile oil. The quantity of volatile oil callus tissues was compared with that of leaves production. Callus was induced from leaf explants on Murashige and Skoog medium (MS) supplemented with Naphthalene acetic acid (NAA) and Benzyl adenine (BA) in different concentrations. Maximum callus fresh weight was obtained in the combination of 10 mg/L BA and 3 mg/L NAA which reached 18 g after four weeks. The results of this work showed that the  quantity of volatile oil from the highest fresh weight callus was 6 ml compared with quantity of 18g of leaves which gave 0.5 ml. Volatile o

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Publication Date
Sun Nov 01 2020
Journal Name
Journal Of Materials Research And Technology
Immobilization of l-asparaginase on gold nanoparticles for novel drug delivery approach as anti-cancer agent against human breast carcinoma cells
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Publication Date
Sat Dec 01 2012
Journal Name
Al Mustansiriyah Journal Of Pharmaceutical Sciences
Formulation and In Vitro Evaluation of Mucoadhesive Antimicrobial Vaginal Tablets of Ciprofloxacin Hydrochloride
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Ciprofloxacin is a broad spectrum fluoroquinolone, effective in the treatment of a wide range of infections, including genitourinary tract infections.In this study, bioadhesive vaginal tablets of ciprofloxacin hydrochloride were prepared by direct compression method using a combination of bioadhesivepolymers carbopol 934P(Cp), carboxymethylcellulose (CMC) and sodium alginate (SA) in different ratios.The prepared tablet formulations were characterized by measuring their swelling capacity, surface pH, bioadhesive properties, and in-vitro drug dissolution. It was found that the bioadhesive force was directly proportional to carbopol 934P content in different formulae and was further enhanced by the inclusion of carboxymethylcellulose.

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