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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
Tue Jun 20 2023
Journal Name
Baghdad Science Journal
Improving propagation of Echinacea purpurea and its content of some active compounds by using Tyrosine and Salicylic acid in vitro
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The seed propagation is the predominant method of Echinacea propagation, which has been criticized for its time-consuming control over the separation factor and the uncertainty of pathogen-free plants produced by this method. The technology of tissue culture has provided multiple opportunities for the production of secondary metabolites continuously without being restricted to a specific season, due to the possibility of controlling the environmental conditions and the components of the nutrient medium needed by the plant. This study was conducted to investigate the effects of salicylic acid as elicitor and tyrosine as precursor on propagation and some secondary compounds production in coneflower in vitro. The result showed the superiori

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Publication Date
Sat Sep 15 2018
Journal Name
Journal Of Baghdad College Of Dentistry
Serum Tumor Necrosis Factor Alpha and High Sensitive C-Reactive protein as Biomarkers in Periodontitis in Iraqi Patients with Osteoarthritis
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Background: Periodontitis (PD) is well-known chronic disease affecting the periodontal ligament and alveolar bone, Osteoarthritis (OA) is a chronic joint disease with compound reasons characterized by synovial inflammation, subchondral bone remodeling, also the formation of osteophytes, that cause cartilage degradation. Chronic periodontitis and osteoarthritis are considered widely prevalent diseases and related to tissue destruction due to chronic inflammation in general health and oral health. The aim of this study is todetermine the association of chronic periodontitis and osteoarthritits in patients by analysing tumor necrosis factor alpha TNFα and high sensitive c-reactive protein (hsCRP) in the serum. Materials and Method: A tot

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Publication Date
Tue Jan 01 2019
Journal Name
Technologies And Materials For Renewable Energy, Environment And Sustainability: Tmrees19gr
The use of cold atmospheric plasma in pentostam enhancement as Leishmaniasis treatment in vitro
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This study illustrates in vitro effect of cold atmospheric plasma (CAP) on the treatment of Leishmania. In addition, the study evaluated the effect of drug treatment (pentostam) and the combination treatment of pentostan and CAP at different doses and incubation time 24 h in order to assess the most effective treatment. The duration of the cold plasma doses was 1 min, 2 min and 3 min, while the pentostam doses were 2.5 µg/ml and 5 µg/ml. The combinations therapies included combining the three cold plasma doses with the pentostam doses to test 6 combinations of treated in vitro. The maximum growth inhibition was given by combination treated 46% and 44% for donovani and tropica leishamnia respectively; these results give an indi

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Publication Date
Sun Sep 07 2014
Journal Name
Baghdad Science Journal
Mixed Ligand Complexes of quinoline-2-carboxylic acid and 4,4/-dimethyl-2,2/-bipyridyl with V(IV),Cr(III), Rh(III), Cd(II) and Pt(IV)
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A new mixed ligand complexes were prepared by reaction of quinoline -2-carboxylic acid (L1) and 4,4?dimethyl-2,2?-bipyridyl (L2) with V(IV),Cr(III), Rh(III), Cd(II) and Pt(IV) ions. These complexes were isolated and characterized by (FT-IR) and (UV-Vis) spectroscopy, elemental analysis, flame atomic absorption technique, thermogravimetric analysis, in addition to magnetic susceptibility and conductivity measurements. Most complexes were mononuclear and with octahedral geometry, except Cd (II) with tetrahedral geometry, and V (IV) with square pyramidal geometry. A theoretical treatment of the ligands and the prepared complexes in gas phase was done using two programs Hyperchem.8 and Gaussian program (GaussView Currently Available Versions (

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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)
Formulation and in vitro /in vivo Evaluation of Silymarin Solid Dispersion- Based Topical Gel for Wound Healing
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Silybum marianum, from which silymarin (SM) is extracted, is a medicinal herb. In the Biopharmaceutics Classification System, it is of the class II type, meaning it is almost completely insoluble in water. It has a number of therapeutic properties, including anti-inflammatory as well as properties that promote wound healing.

This research target is to promote the dissolution and solubility of SM by employing a technique called solid dispersion and then incorporating the formula of solid dispersion into a topical gel that can be used for wound healing.

 

Solid dispersion is a technique used to enhance solubility and dissolve pharmaceuticals that are not water-soluble. This method is widely used because of its low cos

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Publication Date
Fri Feb 28 2020
Journal Name
Neuroquantology
Synthesis, Characterization and Pharmacological Studies of Some New Furosemide Derivatives
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Publication Date
Sun Apr 01 2018
Journal Name
Al–bahith Al–a'alami
‏Framing war against ISIS in New York Times/ from 10/17/2016 to 4/16/2017
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The research is aimed at investigating how the New York Times framed the war against ISIS in its news coverage and which news sources it adopted while reporting on this war.
‏ The research could be classified under descriptive researches. The survey methodology has been adopted and the content analysis has been used. The research sample consists of all the news stories the New York Times have published about the war against ISIS from 10/17/2016 to 4/16/2017 according to the comprehensive sampling method. The number of news stories that were analyzed was (155) news story. The research tool was (coding scheme).
The research has reached the following conclusions:
‏ 1. In its news coverage of the war against ISIS, the New York T

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Publication Date
Sun Sep 15 2024
Journal Name
Iraqi Journal Of Pharmaceutical Sciences( P-issn 1683 - 3597 E-issn 2521 - 3512)
Preparation and In vitro/Ex vivo Evaluation of Nanoemulsion-Based in Situ Gel for Intranasal Delivery of Lasmiditan
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Lasmiditan (LAS) was formulated as a nanoemulsion based in situ gel (NEIG)with the aim of improving its oral bioavailability via application intranasally. The solubility of LAS in oils, emulsifiers, and co-emulsifiers was determined to identify nanoemulsion (NE)components. Phase diagrams were constructed to identify the area of nanoemulsification. LAS NE was formulated using the spontaneous nanoemulsification method. Four NEs (F19, F24, F31, and F34) containing 7-15 % oleic acid (OA) as an oily phase, 40-55% labrasol (LR), and transcutol (TC) as emulsifier mixture at (1:1), (2:1), (3:1), and (1:2) ratio with 30-53 % (w/w) aqueous phase, having suitable optical transparency of 95–98%, globule size of 104-140 nm and polydisper

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Publication Date
Fri Apr 01 2022
Journal Name
Baghdad Science Journal
Colistin as A Good Monotherapy to Restrain the Pathogenicity of Acinetobacter baumannii In vivo and In vitro
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        Acinetobacter baumannii  (A. baumannii) is a major opportunistic nosocomial pathogen, mostly resistant to several groups of antibiotics. Colistin is now used as a last-line treatment for isolates that are highly resistant. The purpose of this study is to identify the importance of LptD; which is involved in the translocation of LPS from the inner membrane to the outer membrane in compartment with LptA and LptC of A. baumannii and its indispensable role as a virulence factor, and the efficiency of colistin as a monotherapy. In the current research, two isolates of A.baumannii were used, the local isolate HHR1 isolated from urine sample and the global strain ATCC 17904, and three antibiot

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Publication Date
Sat Jun 04 2022
Journal Name
Al–bahith Al–a'alami
The Media Image of Afghan Women as Reflected by News Websites in 2021: an Analytical Study of Russia Today site
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International news websites, including Russia Today, pay special attention to the media image of Afghan women, especially after the Taliban movement took control of Afghanistan. Therefore, it was necessary to know the image of the Afghan woman, the fate of the rights she acquired in recent years, and the transformations that affected her after the Taliban took control of the government, and studied them on international news sites, specifically Russia Today.

          The researcher summarized the problem of this study in the following question: What is the media image of the Afghan woman on the Russia Today news site?

         

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