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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 Jan 01 2024
Journal Name
Journal Of Research In Pharmacy
Phytochemical constituents of ethyl acetate fraction of both roots and leaves of Sansevieria triafasciata cultivated in Iraq and assessment of its anti-proliferative effect on breast cancer cell line
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Publication Date
Fri Feb 13 2026
Journal Name
Journal Of Baghdad College Of Dentistry
Elevation in surface temperature of root canals obturated with different thermoplasticized gutta-percha obturation techniques-an in vitro study
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Background: Many studies have been conducted to evaluate the effect of using a hot material in the root canal and its potential for causing damage to the tooth supporting structure. Materials and methods: thirty permanent premolars were obturated with thermoplasticized Gutta-Percha using three different obturation techniques: soft core, Thermafil, and obtura to evaluate the rise in temperature on the root surface using a multipurpose digital thermometer. Results: temperature increases was significantly greater for Obtura versus Soft core (p<0.003), not significant for Thermafil versus Soft core (p<0.087), and Thermafil versus Obtura (p<0.125). Conclusions: temperatures rise on the root surface were below the critical level and, therefore, s

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Publication Date
Fri Feb 13 2026
Journal Name
Journal Of Baghdad College Of Dentistry
The effect of curvature angle and rotational speed on the cyclic fatigue of three types of rotary instrument (In vitro): comparative study
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Background: The fracture of instruments within root canal during endodontic treatment is a common incidence, fracture because of fatigue through flexure occurs due to metal fatigue, this study aimed to assess the effect of curvature angle and rotational speed on the cyclic fatigue of different type of Endodontic NiTi Rotary Instruments and compare among them. Materials and method: Three types of rotary instruments with tip size 0.25: ProTaPer F2 (Densply, Malifier) Revo-S SU( 0.06 taper, MicroMega) and RaCe system (0.06 taper, FKG, Dentaire), Forty file of each instrument were used within two canals with angle of curvature (40 &60 )at two speed (250&400)RPM, twelve group were formed for all instruments(total number=120),ten file fo

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Publication Date
Fri Feb 13 2026
Journal Name
Journal Of Babylon Center For Humanities Studies
Reflection of Zionism in the literature of the Jews of Iraq ... Read in the novel &quot;The Dove Flyer&quot; by Elie Amir
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The upbringing of Yehuda Amichai and the conditions he lived in had a great influence on his deep sense of pain, which made him think of death and suicide. Especially after the Nazis came to power in Germany, and his emigration with his family. Amichai searched for love throughout his life, and his failure was one of the most important factors affecting his psyche, which is A deep influence that made him live in harsh and painful pains that broke him, and prevented her from achieving his ambitions in life.Dramatic texts are characterized by repetition in writing and presentation. It is a textual discourse that has two advantages, first, that it can be read as a literary text like all other literary texts, and second, that it can be consider

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Publication Date
Tue Jun 01 2021
Journal Name
International Journal Of Agricultural And Statistical Sciences
Effect of phosphorous and amino acid on growth and yield of pea
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Publication Date
Sat Dec 11 2021
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Ameliorative Role of Nutraceutical Quercetin and its Derivatives Against Cognitive Impairment Process Induced by Lead Exposure in Drosophila melanogaster(Fruit Fly)
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Cumulative lifetime lead (Pb) exposure has been associated with accelerated declines in cognition through the free radical generation and epigenetic effects. Several pieces of literature have identified a correlation between exposure to lead and neurodegenerative disorders. Harwich strain Drosophila melanogaster was exposed to lead acetate for two weeks, and changes in pulse transmission by acetylcholinesterase and systemic redox were evaluated. Besides, molecular docking studies of acetylcholinesterase against Quercetin and its most common derivatives contained in food have been performed. Pharmacokinetic studies on Quercetin and its derivatives have also been performed in silico toxicity. The data obtained showed alterations in antioxi

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Publication Date
Sat Apr 01 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
In Vitro Release Study on Capsules and Tablets Containing Enteric - Coated Granules Prepared by Wet Granulation
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Wet granulation method was used instead of conventional pan coating  or fluidized –bed coating technique to prepare enteric-coated diclofenac sodium granules, using ethanolic solution of EudragitTM L100 as coating, binding and granulating agent .Addition of PEG400 or di-n-butyl phthalate as a plasticizer was found to improve the enteric property of the coat.

Part of the resulted granules was filled in hard gelatin capsules (size 0), while the other part was compressed into tablets with and without disintegrant.

The release profile of these two dosage forms in 0.1N HCl (pH 1.2)for 2 hours, and in phosphate buffer (pH 6.8) for 45 minutes as well as the release kinetic were compared with that of the en

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Publication Date
Fri Aug 28 2020
Journal Name
Iraqi Journal Of Science
Callus Induction and Shoot Formation for Mexican Red Bean (Phaseolus vulgaris L.) Pinto Cultivar in Vitro
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The current study aimed to adopt a method for inducing callus cells and regenerating the important common red bean using different types of growth regulators such as N6-benzylaminopurine (BAP), Naphthalene acetic acid (NAA), and Thidiazuron (TDZ). Different types of common bean pinto cultivar explants, such as internodes, cotyledons and roots, were inoculated on Murashige and Skoog medium (MS) provided with different combinations of plant growth regulators, including 1- BAP (5 mg/l) 2-BAP (4.5 mg/l) NAA (0.5 mg/l), 3- BAP (4.5 mg/l), and TDZ (0.1mg/l). Callus was initiated on MS culture medium supplied with 5 mg/l BAP for all explants (internodes, cotyledons, and roots) at 50, 20, and 10% respectively, while adding NAA with 0.5mg/l showed

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Publication Date
Wed Mar 24 2021
Journal Name
Indian Journal Of Forensic Medicine &amp; Toxicology
Evaluating the anti- Pseudomonas Aeroginosa Efficacy and Potential Cytotoxicity of Nerium Oleander Alcoholic Extract
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Nerium oleander known as oleander has belonged to the poisonous plants its habitat in a tropical andsubtropical region. The chemical analysis with GC-Mass of the alcoholic extract of oleander leaves revealedthat this plant has many chemical compounds more than 80 compounds and high-peaks about 29 compoundswhich are represented by alkaloids, phenol, terpenes, and fatty acid. HPLC analysis showed many essentialoils that have many biological effects.To evaluate the antibacterial activity of the alcoholic extract of N. oleander against locally isolatedPseudomonas aeroginosa the broth micro-dilution method was adapted to different concentrations werestarted from 3.9 to1000 mg/ml. The results revealed that the alcoholic extract has antiba

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Publication Date
Mon Jan 01 2018
Journal Name
Indian Journal Of Public Health Research &amp; Development
Effect of salpingectomy on anti müllerian hormone, follicle-stimulating hormone and inhibin b hormone
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