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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
Sat Jun 19 2021
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
The Pharmacological Effects of Kappa Carrageenan on Different Human Cell Lines and Genomic DNA: An in vitro study
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Carrageenan extract is a compound of sulfated polyglycan that is taken out from red seaweeds. Being hydrocolloid in nature, carrageenan has gelling, emulsifying and thickening properties allowing it to be commonly used in the oral healthcare products and cosmetics. Due to its bioactive compounds, carrageenan has been shown to have antimicrobial, antiviral, and antitumor properties. The purpose of this work is to study the probable use of carrageenan on the diseases that are related to oral cavity and on the genomic DNA in in vitro experimental model

In this study, the effects of k-carrageenan on four different cell lines related to the cancer and normal cells which cultured on selective media were done. Moreover, the eff

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Publication Date
Thu Jul 20 2023
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
In Vitro Effect of Mannitol Stress and γ-ray on Secondary Products From Golden Sunrise Cherry Tomato Callus
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Effect of drought stress induced by mannitol on secondary products in callus of Golden Sunrise cherry tomatoes were studied in vitro. Seeds were irradiated with gamma at the doses (0, 20, or 40 Gy), and germinated on Murashige and Skoog, (MS) basal medium. Callus were initiated from cotyledon leaf explants using a combination of (2.0 kin + 2.0 IAA mg. l-1) then transferred into MS medium supplemented with mannitol at concentrations of (0, 40, and 60 g.l-1). Vitamin C(vit C), enzyme activity, Ascorbate peroxidase (Apx), and Amylase  enzymes, Proline amino acid and β- carotene were quantified by high-performance Performance Liquid Chromatography (HPLC). Results revealed that, highest contents of (Apx) 128.16 µg. m

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Publication Date
Thu Sep 30 2021
Journal Name
Iraqi Journal Of Science
Evaluating the in vitro Cytotoxicity of Thymus vulgaris Essential Oil on MCF-7 and HeLa Cancer Cell Lines
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     Thyme essential oil (TEO) was extracted from dried leaves of Thymus vulgaris. The air-dried aerial parts of the plant produced 1.0% yield of TEO. The detection of this essential oil’s compounds was performed by GC-MASS. The cytotoxic activity of TEO was evaluated against two human cancer cell lines, namely HeLa (human epithelial cervical cancer) and MCF-7 (human breast carcinoma). Cells grown in 96 multi-well plates were treated with six concentrations of EO (6.25, 12.5, 25, 50, 100, 200 ppm) and incubated at 37 °C for 72 hrs. Cancer cell lines elicited various degrees of sensitivity to the cytotoxic effect of essential oil. The TEO exhibited significant differences (p≤ 0.01) between the effects of

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Publication Date
Mon Aug 22 2016
Journal Name
Journal Of Natural Sciences Research
In Vitro Cytotoxic Effect of Aqueous Extract of Origanum Marjoram on AMN-3 Cell Line
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Publication Date
Wed Feb 05 2025
Journal Name
Journal Of Baghdad College Of Dentistry
The Effect of Zinc Oxide Nanoparticles on Streptococcus mutans of Human Saliva (In Vitro Study)
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Background: Nanotechnology represents a new science that promises to provide a broad range of uses and improved technologies for biological and biomedical applications. One of the reasons behind the intense interest is that nanotechnology permits synthesis of materials that have structure is less than 100 nanometers. The present work revealed the effect of zinc oxide nanoparticles (ZnO NPs) on Streptococcus mutans of Human Saliva in comparison to de-ionized water. Materials and methods: Streptococcus mutans were isolated from saliva of forty eight volunteers of both sexes their age range between 18-22 years and then purified and diagnosed according to morphological characteristic and biochemical tests. Different concentrations of ZnO NPs w

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Publication Date
Wed May 17 2017
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
Antibacterial Effect of Lawsonia inerims linn. (Henna) Using Three Types of Leaf Extract In Vitro
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  This study was done to investigate the antibacterial effect of the three types of Lawsonia inermis linn (henna) leaf extracts (water, methanol and chloroform) in different concentrations (40, 80, 120) mg/ml against four strains of bacteria (Staphyllococus aureus, Bacillus subtilis, Pseudomonos aerogenosa and Eschorichia coli) in vitro using ager well diffusion method. Water extract showed the highest antibacterial activity, followed by  methanol extract, while the chloroform extract showed the lowest activity. The maximum inhibition zone of water extract was observed against , Pseudomonos aerogenosa (25mm) in the concentration (120) mg/ml, while the minimum zone of inhibition (9mm) was in Bacillus subtilis in the same concent

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Publication Date
Thu Dec 28 2017
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
Study the Effect of Alcoholic Extract of Nigella sativa Seeds on Trichomomas vaginalis In Vitro
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 The present study included experimental effect of Metronidazole drug and Alcoholic extract of Nigella sativa seeds on T. vaginalis that cultivated on  i               i    Results showed that the numbers of parasite began increasing during a period after 24-48 hrs then began decreasing after 72-96 hrs, so that 72 hrs from growth considered logarithmic phase of T. vaginalis growth. Present results showed poisonous effect of N. sativa alcoholic extract that was prepared in laboratory and imported at concentrations (450, 550, 650 and 750) mg/ml on T. vaginalis by observing gradual decrease of trophozoite numbers with concentrate increase of extra

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Publication Date
Wed Feb 08 2023
Journal Name
Iraqi Journal Of Science
Increasing of Some Medical Flavonoid Compounds of Dodonaea viscosa L. using AgNO3 Nanoparticles In Vitro
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The research was conducted to study the effect of adding different concentrations of AgNo3 Nanoparticles (0,0.5,1.0,1.5,2.0) mg/ l in the production of some secondary metabolic compounds(Quercetin, Luetolin and Apigenin) of plant Dodonaea viscosa L. Quantitative and qualitative analysis of secondary metabolites were estimated by using( HPLC ). The explants from leaves were culture on MS media supplemented with 2mg/l of 2,4-D, 0.5mg/l of NAA and 0.5 mg/l of BA for callus induction. Adding AgNo3 Nanoparticles (2 mg/l) cause in significant increase of Quercetin and Luetolin production, while adding AgNo3 Nanoparticles (0.5mg/l) led to significant increase of Apigenin in callus extract.

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Publication Date
Wed Jan 01 2014
Journal Name
The Scientific World Journal
An In Vitro Assessment of Gutta-Percha Coating of New Carrier-Based Root Canal Fillings
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The first aim of this paper was to evaluate the push-out bond strength of the gutta-percha coating of Thermafil and GuttaCore and compare it with that of gutta-percha used to coat an experimental hydroxyapatite/polyethylene (HA/PE) obturator. The second aim was to assess the thickness of gutta-percha around the carriers of GuttaCore and HA/PE obturators using microcomputed tomography (μCT). Ten (size 30) 1 mm thick samples of each group (Thermafil, GuttaCore, and HA/PE) were prepared. An orthodontic wire with a diameter of 0.5 mm was attached to the plunger of an Instron machine in order to allow the push-out testing of the gutta-percha coating. Five samples of (GuttaCore and HA/PE) were scanned using

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Publication Date
Mon Mar 08 2021
Journal Name
Baghdad Science Journal
PREPARATION OF NITRATION DERIVATIVES OF BILE SALTS AND ACIDS FOR MEDICAL USE
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The derivatives formed after the successive acetylation, esterification and nitration reactions to cholic, deoxycholic, and taurocholic acids were identified to be of the following general strucure: Colt, Where RI=NO3, OH, 0=, or CH3COO. R2=H, NO3, OH, 0-=, or CH3COO. R3=H, NO3,01-1, 0=, or CH3COO. R4=OH, NH(CH2)2S03Na, NH(CH2)2S03H, or OMe. By using U.V-visible and I.R spectrophotometry . The number of hydroxyl groups was determined, purity was checked from T.L.C, Most of these derivatives will find pharmaceutical application.

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