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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
Thu Jan 01 2015
Journal Name
International Journal Of Technical Research And Applications
SYNTHESIS OF DRUG CARRIER POLYACRYLIC ACID WITH SPACER GROUP
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Publication Date
Sun Feb 03 2019
Journal Name
Journal Of The College Of Education For Women
The Yamanies Service to al- Haj between the 4 – up to 9 centuries A.H.
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The Yemen Kings and gaverners allered notable services to the pilgrims, who
were in their way to perform the pilgrimage to Mecca. Among them Al-Hysen Ibn
Salama (dead 384, Aih). The governer of Al- Zeadiea state, who concern about
pilgrimage route from its beginning at Hudrumot to its end at Mecca Al Makruma, the
distant was estimated by 60th days to pass the way he also eastablished asystem of
water “artesian wells” as long as the pilgrimage way also setting up large Mosqeses
and Marking out the way of the caravans of pilgrimage to save these caravans from
lossing the right way, he setting up under ground water chanal started from Arafat to
holy Mecca in order to ensure water supplies for the erea. This proje

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Publication Date
Sun May 10 2015
Journal Name
Al-academy
Functionalizing Location's Indications and Aesthetic Elements in Novel Film"(Pianist Film as an example): منير طه سلمان
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Cinema artist work has not been achieved without location indications ; places are of cultured indications and its effect on behaviors and trends. Location is an important element as to convey meanings via its interaction with the personality about which it has been written may studies. Despite location occupies huge spaces within social and philosophical Drama branches , but it has a strong connection with the art world since it reflects reality of global theories in different fields. Audio and visual speech in Cinema have connected with the environmental effectiveness resulted from location which the sensual understanding interacts with in a way that suits Movie. Location consists of mixing elements of Movie and it in return interacts

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Publication Date
Mon Aug 11 2025
Journal Name
Scientific Reports
An in vitro evaluation of the mineralization effect of a marine collagen supplement on early enamel lesions
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The marine collagens are biocompatible and biodegradable materials that are considered as a biomimetic approach for tissue regeneration. This study evaluated the effect of daily consumption of marine collagen supplement drink on enamel white spot lesions (WSLs), comparing the results against Regenerate system and Sylc air abrasion methods. Fifty human enamel slabs were allocated into five groups (n = 10 per group): non-treated (sound); non-treated (WSLs, 8% methylcellulose gel with 0.1 M lactic acid (pH 4.6) at 37 °C for 21 days); and three treated surfaces with marine collagen; Regenerate system; and Sylc air abrasion. The treatment lasted for 28 days followed by four weeks’ storage in artificial saliva (pH = 7.0, 37 °C). Evalu

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Publication Date
Thu Oct 31 2019
Journal Name
Asian Journal Of Pharmaceutical And Clinical Research
DESIGN, SYNTHESIS, DOCKING, ANTITUMOR SCREENING, AND ABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION PREDICTION OF NEW HESPERDIN DERIVATIVE
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Objective: Hesperidin (HSP) is a pharmacologically active organic compound found in citrus fruits and peppermint. We synthesized a new HSP derivative by reacting it with 5-Amino-1,3,4-thiadiazole-2-thiol in acetic acid. Methods: This compound was characterized by Fourier-transform infrared, proton nuclear magnetic resonance, and electron impact mass spectra. A molecular docking study explores the predicted binding of the compound and its possible mode of action. Bioavailability, site of absorption, drug mimic, and topological polar surface was predicted using absorption, distribution, metabolism, and excretion (ADME) studies. Results: The docking study predicts that the new compound binds to the active sites of Aurora-B

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Publication Date
Sun Dec 01 2019
Journal Name
Journal Of Medicinal And Chemical Sciences
Synthesis and Identification of New 2-Substituted-1,3,4-Oxadiazole Compounds from Creatinine and Study Their Antioxidant Activities
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Publication Date
Sat Dec 31 2022
Journal Name
International Journal Of Dentistry
Bond Strength Survival of a Novel Calcium Phosphate-Enriched Orthodontic Self-Etching System after Various Ageing Protocols: An In Vitro Study
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Objective. This study aimed to evaluate the orthodontic bond strength and enamel-preserving ability of a hydroxyapatite nanoparticles-containingself-etch system following exposure to various ageing methods. Materials and Methods. Hydroxyapatite nanoparticles (nHAp) were incorporated into an orthodontic self-etch primer (SEP, Transbond™ plus) in three different concentrations (5%, 7%, and 9% wt) and tested versus the plain SEP (control) for shear bond strength (SBS), adhesive remnant index (ARI) scores, and enamel damage in range-finding experiments using premolar teeth. The best-performing formulation was further exposed to the following four artificial ageing methods: initial debonding, 24 h water storage, one-month water stora

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Publication Date
Sun Jun 01 2008
Journal Name
Baghdad Science Journal
A New Derivatives of Benzodiazepine, Imidazole, Isatin, Maleimide, Pyrimidine and 1,2,4-Triazole: Synthesis and Characterization
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The synthesis of new benzodiazepine, imidazole, isatin, maleimide, pyrimidine and 1,2,4-triazole derived from 2-amino-4-hydroxy-1,3,5-triazine, via its cyclocondensation reaction with different organic reagents, is described. FT-IR, 1H-NMR and as well as 13C-NMR spectra disclosed the structures of the precursors and heterocyclic derivatives formed.

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Publication Date
Thu Jan 01 2009
Journal Name
Ibn Al- Haitha M J. Fo R Pur E & Appl. Sc I
Synthesis and Structural Study of Some Mo(II) Carbonyl Complexes with Triazole and Oxadiazole Derivatives
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A new carbonyl complexes of triazole and oxadiazole were synthesized. These complexes were identified and their structural geometric were suggested by using FT-IR and UV-Vis spectra, conductivity measurements and other chemical and physical properties. The spectra data (FT-IR, UV, Vis.) with the substantial aid of group theoretical calculations gave so many evidences for the proposed geometries and the type of bonding of these compounds

Publication Date
Thu Feb 01 2024
Journal Name
Russian Journal Of Bioorganic Chemistry
Synthesis, Characterization of Formazan Derivatives from Isoniazid and Study Their Antioxidant Activity and Molecular Docking
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Objective: Synthesis, Characterization of formazan derivatives and studies the antioxidant activity of prepared compounds and molecular docking. Methods: In this study, formazan compounds (III–XIV) were produced by combining Schiff base compounds (I), (II) with diazonium salts resulting from reactions of different aromatic amines with sodium nitrate in the presence of Con.HCl at 0–5°C. When isonicotinic acid hydrazide reacts with (N,N-dimethylbenzaldehyde, 4-hydroxy-3-methoxybenzaldehyde) in the presence glacial acetic acid as a solvent Schiff base compounds are created. Results: The prepared compounds were identified by FT-IR, 1H NMR, 13C NMR, then the antioxidant activity of the derivatives and molecular docking were studied. D

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