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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 Dec 24 2022
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Neuroprotective Effect of Vinpocetine against Lead Acetate-Instigated Neurotoxicity in Rats by Evaluation Tumor Necrosis Factor-Alpha, Interleukin-1Beta and Interleukin-10
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Lead toxicity elicits neurological damage which is a well-known disorder that has been considered to be a major cause for multiple condition such as behavioral defect; mental retardation; and nerve insufficient activity.

This research is designed to estimate potential protective effect of vinpocetine on neurotoxicity stimulated by lead acetate in rats.

Eighteen adult rats of both sexes were randomly enrolled into three groups. Each group includes 6 rats as followings: Group I- Rats were given 0.3ml normal saline solution orally; then intraperitoneal injection of 100μl of the normal saline was given 1h later; this group was considered as control. Group II- Rats were given an intraperitoneal injection of 20mg/kg lead acetate

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Publication Date
Sat Dec 31 2011
Journal Name
Al-khwarizmi Engineering Journal
Effect of Mixed Corrosion Inhibitors in Cooling Water System
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The effect of mixed corrosion inhibitors in cooling system was evaluated by using carbon steel specimens and weight loss analysis. The carbon steel specimens immersed in mixture of sodium phosphate (Na2 HPO4) used as corrosion inhibitor and sodium glocunate (C6 H11 NaO7) as a scale dispersant at different concentrations (20,40, 60, 80 ppm) and at different temperature (25,50,75 and 100)ºC for (1-5) days. The corrosion inhibitors efficiency was calculated by using uninhibited and inhibited water to give 98.1%. The result of these investigations indicate that the corrosion rate decreases with the increase the corrosion inhibitors concentration at 80 ppm and at 100ºC for 5 days, (i.e,

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Publication Date
Wed Jan 28 2026
Journal Name
Journal Of Baghdad College Of Dentistry
Evaluation of en-masse retraction using microimplant versus conventional techniques: An in vitro study
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Background: The study aimed to investigate the effect of different techniques of en masse retraction on the vertical and sagittal position, axial inclination, rate of space closure, and type of movement of maxillary central incisor. Materials and methods: A typodont simulation system was used (CL II division 2 malocclusion). Three groups were used group 1(N=10, T-loop), group 2(N=10, Time-Saving loop), and group 3(N=10, Microimplant). Photographs were taken before and after retraction and measurements were made using Autodesk AutoCAD© software 2010. Kruskal-Wallis one-way analyses of variance and Mann-Whitney U test (p?0.05) were used. Results: The rate of space closure showed no significant difference among the three groups (p?0.05), whi

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Publication Date
Mon May 01 2023
Journal Name
Iop Conference Series: Earth And Environmental Science
Screening and optimization of a novel gallic acid and tannase production under semi quantitative and quantitative methods
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Abstract<p>Tannin acyl hydrolase as the common name of tannase is an inducible extracellular enzyme that causes the hydrolysis of galloyl ester and depside bonds in tannins, yielding gallic acid and glucose. The main objective of this study is to find a novel gallic acid and tannase produced by <italic>Acinetobacter Baumannii</italic>. A number of optimization steps were followed in order to improve the highest production of gallic acid and tannase. In present study, <italic>A. baumannii</italic> were isolated from ICU burn. <italic>A. baumannii</italic> was examined by microscopic examination, morphological and biochemical assay including oxidase and catalase. The </p> ... Show More
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Publication Date
Tue Feb 02 2021
Journal Name
International Journal Of Pharmaceutical Research
Antimicrobial Evaluation of Some New Synthesized NHydroxy Phthalimide Derivatives
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In this work, N-hydroxy phthalimide derivatives (NHPID) were synthesized from the nucleuphilic substitution reactions of (NHPI) with different halides (alkyl halides, sulfonyl halides, benzoyl halides and benzyl halides). The products were distinguished using FTIR spectrum and Nuclear magnetic resonsnce (1H-NMR and 13CNMR), in addition to other characteristic methods such as sodium fution for sulfur determination. followed by measuring antibacterial (with different types of gram positive/gram negative bacteria) and antifungal activities of these compounds.

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Publication Date
Mon Sep 30 2024
Journal Name
Iraqi Journal For Applied Sciences
Examining Metal Complexes Formed from New Schiff Base ‎Ligand ‎Derived from Benzene Carbaldehyde: Evaluation of Anti-‎biofilm and ‎Anti-bacterial Properties
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One of the most difficult tasks in modern medical societies is the process of identifying a cure for many infectious diseases caused by drug-resistant microbes. Therefore, it has become necessary to discover new compounds that work in this regard. The currently prepared Schiff base, derived from thiazole, has a biological activity against bacteria and biofilms and its activity increases when it is associated with copper, zinc and platinum ions and forms metal complexes. This study highlights the synthesis and evaluation of novel biological compounds as inhibitors of bacterial growth and biofilms. A three newly complexes are resulting from the reaction of a new Schiff base ligand (LC) with metal ions (Zn, Cu, Pt). The new ligand (LC)

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Publication Date
Wed Jan 28 2026
Journal Name
Journal Of Baghdad College Of Dentistry
Evaluation of antibacterial action of photosensitizer solution activated by diode lamp and three intracanal medicaments (in vitro study)
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Background: The elimination of the microorganisms from the root canal systems, an important step for the successful root canal treatment. This study was conducted to evaluate the antibacterial effectiveness of the photoactivated disinfection by using the toluidine blue O and a low- energy light emitting diode (LED) lamp . Materials and method: Sixty single rooted extracted teeth were decoronated, instrumented, irrigated, sealed at the apex and contaminated with endodontic anaerobic bacteria for 7 days to form biofilms in prepared root canals. Group I. Twelve teeth were medicated by photosensitizer (toluidine blue O) solution activated by diode lamp (FotoSan; CMS Dental, Copenhagen, Denmark).Group II. Twelve teeth were medicated by the tricr

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Publication Date
Sun Apr 01 2012
Journal Name
Journal Of Educational And Psychological Researches
Effectiveness of at site electronic learning/teaching in educational development
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 This study investigated three aims for the extent of effectiveness of the two systems in educational development of educators. To achieve this, statistical analysis was performed between the two groups that consisted of (26) participants of the electronic teaching method and (38) participants who underwent teaching by the conventional electronic lecture. The results indicated the effectiveness of the “electronic teaching method” and the “electronic lecture method” for learning of the participants in educational development. Also, it indicated the level of equivalence from the aspect of effectiveness of the two methods and at a confidence level of (0.05). This study reached several conclusions, recommendations, and suggestio

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Publication Date
Fri Jan 12 2024
Journal Name
Jornal Brasileiro De Patologia E Medicina Laboratorial
Synthesis, Characterization, and Potential Biomedical Applications of Novel Symmetrical Liquid Crystal Mesogens
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Background: The synthesis and characterization of novel liquid crystalline compounds have garnered signi|cant attention due to their potential applications in biomedical sciences, including drug delivery systems, biosensing, and diagnostic tools. This study focuses on synthesizing and characterizing new thiazolothiadiazole-based liquid crystals and evaluating their mesophase properties. Methods: A series of novel compounds containing 5H-thiazolo[4,3−b][1,3,4] thiadiazole units were synthesized via multi-step chemical reactions. The synthesis involved the reaction of chloroethyl acetate with 4−hydroxybenzaldehyde to yield an aldehyde intermediate, followed by subsequent transformations using hydrazine hydrate, ethylacetoacetate, and 1,2

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Publication Date
Tue Jul 18 2017
Journal Name
Inorganica Chimica Acta
Synthesis, characterization and liquid crystalline properties of novel benzimidazol-8-hydroxyquinoline complexes
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The synthesis, characterization and liquid crystalline properties of N4,N40-bis((1 H-benzo[d]imidazol-2- yl)methyl)-3,30-dimethyl-[1,10-biphenyl]-4,40-diamine and of their corresponding Mn(II), Fe(II), Ni (II), Cu(II), and Zn(II) complexes are described. The ligand and complexes have been characterized by elemental analysis, magnetic susceptibility measurements (meff), conductometric measurements and Fourier Transform Infrared (FTIR), Nuclear Magnetic Resonance (1H NMR), (13C-NMR) and UV–Vis spectroscopy. Spectral investigations suggested octahedral coordination geometrical arrangement for M(II) complexes. The phase transition temperatures were detected by differential scanning calorimetry (DSC) analysis and the phases are confirmed by op

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