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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 Jun 30 2016
Journal Name
Al-kindy College Medical Journal
Evaluation Of Risk Factors In Perforated Acute Appendicitis In Al-Kindy Teaching Hospital
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Background: Appendectomy is still one of the most commonly performed emergency surgical procedures worldwide.Avoiding delays in the diagnosis in these patients may play a role in reducing observed morbidity.Aim of study:To analyze the clinico-pathological profile and outcomes of patients undergoing emergency appendectomies to determine risk factors influencingcomplicaions.Type of the study: A prospective analytic studyPatients and Methods: The study involves 108 patients underwent emergency appendectomies at Al-kindy teaching hospital from April 2014 to March 2015. Appendicitis was categorized into two groups perforated andnonperforatedappendicities. A comparison between them was made in regard to Gender, Age, clinical presentation, inve

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Publication Date
Wed Jun 11 2025
Journal Name
Biomedical Reports
Valproic acid exposure alters histone deacetylase mRNA expression profile in oral cancer and premalignant cell lines
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Publication Date
Mon Mar 15 2021
Journal Name
Journal Of Baghdad College Of Dentistry
Efficacy of arthrocentesis with injection of hyaluronic acid in the treatment of inflammatory-degenerative disease of temporomandibular joint
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Background:Temporomandibular joint (TMJ) problems refer to a group of heterogeneous pain and dysfunction conditions involving the mastication, reducing life quality of the patients. Arthrocentesis is a simple and less invasive surgical method for the treatment of inflammatory-degenerative disease than other conservative procedures and better than arthroscope. This clinical study aimed at evaluating the benefit of arthrocentesis with injection of hyaluronic acid in the management of inflammatory-degenerative disease of the TMJ. Material and methods: Eighty consecutive patients were enrolled in this study with pain symptoms of TMJ, insufficient masticatory efficiency during function and limitation of mouth opening; they were assessed with

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Publication Date
Mon Oct 01 2012
Journal Name
Journal Of Engineering
Prediction of Smear Effect on the Bearing Capacity of Driven Piles
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This paper deals with prediction the effect of soil re-moulding (smear) on the ultimate bearing capacity of driven piles. The proposed method based on detecting the decrease in ultimate bearing capacity of the pile shaft (excluding the share of pile tip) after sliding downward. This was done via conducting an experimental study on three installed R.C piles in a sandy clayey silt soil. The piles were installed so that a gap space is left between its tip and the base of borehole. The piles were tested for ultimate bearing capacity according to ASTM D1143 in three stages. Between each two stages the pile was jacked inside the borehole until a sliding of about 200mm is achieved to simulate the soil re-moulding due to actual pile driving. The re

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Publication Date
Sat Oct 06 2012
Journal Name
Journal Of Engineering
Prediction of Smear Effect on the Bearing Capacity of Driven Piles
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Publication Date
Sat Jul 22 2023
Journal Name
Journal Of Engineering
Prediction of Smear Effect on the Bearing Capacity of Driven Piles
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This paper deals with prediction the effect of soil remoulding (smear) on the ultimate bearing capacity of driven piles. The proposed method based on detecting the decrease in ultimate bearing capacity of the pile shaft (excluding the share of pile tip) after sliding downward. This was done via conducting an experimental study on three installed R.C piles in a sandy clayey silt soil. The piles were installed so that a gap space is left between its tip and the base of borehole. The piles were tested for ultimate bearing capacity
according to ASTM D1143 in three stages. Between each two stages the pile was jacked inside the borehole until a sliding of about 200mm is achieved to simulate the soil remoulding due to actual pile driving. T

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Publication Date
Tue Jun 01 2021
Journal Name
Al-khwarizmi Engineering Journal
Prediction of Surface Roughness after Turning of Duplex Stainless Steel (DSS)
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Feed Forward Back Propagation artificial neural network (ANN) model utilizing the MATLAB Neural Network Toolbox is designed for the prediction of surface roughness of Duplex Stainless Steel during orthogonal turning with uncoated carbide insert tool. Turning experiments were performed at various process conditions (feed rate, cutting speed, and cutting depth). Utilizing the Taguchi experimental design method, an optimum ANN architecture with the Levenberg-Marquardt training algorithm was obtained. Parametric research was performed with the optimized ANN architecture to report the impact of every turning parameter on the roughness of the surface. The results suggested that machining at a cutting speed of 355 rpm with a feed rate of 0.07 m

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Publication Date
Sun Sep 25 2022
Journal Name
Hiv Nursing
BIOSYNTHESIS OF SILVER / SILVER CHLORIDE NANOPARTICLES BY IRAQI PROPOLIS AND STUDY THE ANTI – BACTERIAL ACTIVITY
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Sliver / Sliver chloride is as old used from human but the sliver / sliver chloride nanoparticles have only recently been recogenized. They have used in medicin and agiculture. In the present study have been investigation the effecte biosynthesis Sliver / Sliver chloride nanoparticles as antibacterial by demonstrated that Ag / AgCl NPs arrest the growth of many bacterial: S.typhimurium, k. pneumonia. S. aureus, L.monocytogenes, B. Anthracis, E. coli, C. frundi, S. Pneumonia, P. Aeruginosa. The elements compestion and crystallization panal of biosynthesized nanoparticles were chracterazated by FTIR, XRD and SEM. From XRD, It is confirmed the synthesized nanoparticles contain Sliver / Sliver chloride elements. Synthesized Ag / AgCl NPs showed

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Publication Date
Sun Sep 15 2019
Journal Name
Journal Of Global Pharma Technology
Effect of Citric Acid Application on Anatomical and Physiological Properties of the Vegetative Parts of a Species of Tamarindus Indica Cultivated in Iraq
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Publication Date
Sun Jan 01 2023
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
Preparation, Structural Characterization and Biological Activities of Curcumin-Metal(II)-L-3,4-dihydroxyphenylalanin(L-dopa)complexes
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In the present work, a first-row divalent d-transition metal obtained from curcumin(Curc) and L-3,4-dihydroxyphenylalanin(L-dopa)have been synthesized which their complexes and characterized by C.H.N, conductance, spectral methods: FT-IR, Ultra–Visible. Magneto-chemical measurements, molar conductance ΛM (1×10−3 mol/L in DMSO):36- 0.84 ohm-1.cm2.mol-1 (non-electrolyte). The data shows that the complexes have the structure [M((II))-(Curc)-(L-dopa)] system. Electronic and magnetic data suggest an octahedral geometry for all complexes in which the (L-dopa) and curcumin act as bidentate ligands. Curcumin coordinated to the metal ions M (II) through the lone pair of electrons of oxygen in 2(C=O) groups. The (L-dopa) coordinated to M (II) a

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