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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
Wed Aug 30 2023
Journal Name
Al-kindy College Medical Journal
Pancreatic Stone Protein/ regenerating Protein (PSP/reg) as a Biochemical Marker for prediction of Microvascular Complications of Type 2 Diabetes Mellitus
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Background: Type 2 diabetes mellitus (T2DM) characterized by insulin resistance (IR) and progressive decline in functional beta (β) cell mass partially due to increased β cell apoptosis rate. Pancreatic stone protein /regenerating protein (PSP/reg) is produced mainly by the pancreas and elevated drastically during pancreatic disorder. Beta cells are experiencing apoptosis that stimulate the expression of PSP/reg gene in surviving neighboring cells, and that PSP/reg protein is subsequently secreted from these cells which could play a role in their regeneration.

Objectives: To analyze serum levels of PSP/reg protein in T2DM patients and evaluate its correlation with the microvasc

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Publication Date
Thu Jul 23 2026
Journal Name
Journal Of Baghdad College Of Dentistry
The Electrophoretic Deposition of Nano Al2O3 and AgNO3 on CpTi Dental Implant (An in vitro and in vivo study)
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Background: Even the wide use of dental implants, still there is a proportion of implants are failed due to infection. Much considerable attention has been paid to modify the implant surface. Coating of dental implant with a biocomposite material of suitable properties can improve osseointegration. And this is the main concern of this study. The aim of present study was to evaluate the use of a biocomposite coating of dental implant with (ceramic nano Al2O3 and metalic AgNo3) on the bond strength at bone – implant interface and tissue reaction. Materials and methods: A total number of forty-eight screws, CpTi dental implant used in this study. Half of these screws were coated with a biocomposite material of nano (Al2O3and AgNo3), thi

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Publication Date
Sun Aug 20 2023
Journal Name
International Journal Of Drug Delivery Technology
Role of higB-higA Novel Genes in Antibiotics Resistance of Pseudomonas aeruginosa
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Background: Pseudomonas aeruginosa is a devious pathogen with the tendency to prompt many acute and serious chronic diseases. This study aims to detect novel genes (Toxins-Antitoxins II system), especially; higB and higA encoded from P. aeruginosa by PCR technique and the relation between these genes and antibiotic resistance of P. aeruginosa. Methods: This study detected 50 isolates of P. aeruginosa from distinct clinical sources. The most common origin of isolates was (44%) burn swabs, (22%) urine culture, (12%) wound swabs, (14%) sputum, and (8%) ear swabs. The bacteria were isolated using implantation MacConkey agar and blood agar, as well as biochemical tests including oxidase test, catalase test then VITEK-2 System of P. aerug

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Publication Date
Sat Jun 18 2022
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Anti-Inflammatory Activity of Gingko Biloba Extract in Cotton Pellet-Induced Granuloma in Rats: A comparative Study with Prednisolone and Dexamethasone
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The current study was designed to evaluate the anti-inflammatory effect of GKB in the rat model of granulomatous inflammation. Thirty rats were distributed into five groups:  The first group served as negative control group that received distilled water (DW) only without inducting inflammation, positive control group; treated with DW with the induction of inflammation and they were assigned to cotton pellet-induced granuloma, ginkgo biloba (GKB) treated group (200mg/kg/day), dexamethasone-treated group (1mg/kg), and Prednisolone treated group (5mg/kg). All the treatments were given orally for seven consecutive days.  On day eight, the rats were anesthetized and the pellets together with granulation tissue were carefully removed

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Publication Date
Thu Jan 01 2015
Journal Name
Chemistry And Materials Research
Synthesis, Physico-Chemical and Antimicrobial Activities Co(II),Ni (II) ,Cu(II), Zn(II),Cd(II) and Hg(II) Mixed- Ligand Complexes of L- Alanine and Trimethoprim Antibiotic
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The Co (II), Ni (II) ,Cu(II), Zn(II) ,Cd(II) and Hg(II) complexes of mixed of amino acid (L-Alanine ) and Trimethoprim antibiotic were synthesized. The complexes were characterized using melting point, conductivity measurement and determination the percentage of the metal in the complexes by flame (AAS). Magnetic susceptibility, Spectroscopic Method [FTIR and UV-Vis]. The general formula have been given for the prepared mixed ligand complexes [M(Ala)2(TMP)(H2O)] where L- alanine (abbreviated as (Ala ) = (C5H9NO2) deprotonated primary ligand, L- Alanine ion .= (C5H8NO2 -) Trimethoprim (abbreviated as (TMP ) = C10H11N3O3S M(II) = Co (II),Ni(II) ,Cu(II), Zn(II) ,Cd(II) and Hg(II). The results showed that the deprotonated L- Alanine by KOH (Ala

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Publication Date
Tue Jun 01 2021
Journal Name
Journal Of Advanced Joining Processes
Coupled Eulerian–Lagrangian prediction of thermal and residual stress environments in dissimilar friction stir welding of aluminum alloys
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The evaluation of residual stresses (RS) induced by the friction stir welding (FSW) process is crucial in anticipating the performance of the welded structure. The existence of such residual stresses within a friction stir welded structure may lead to excessive distortion and weakness to afford the applied external loads. To assess quantitatively the effect of these residual stresses generated by FSW process, the current paper implements a Coupled Eulerian–Lagrangian (CEL) finite element simulation to analyze both thermal and subsequent resulted remaining stress environments in dissimilar friction stir welding of AA6061-T6 and AA2024-T3 alloys. The thermal analysis step was conducted first and followed by a mechanical analysis step in whi

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Publication Date
Fri Dec 15 2023
Journal Name
Al-adab Journal
The Portrayal of Serial Killers in Thomas Harris’ Novel Read Dragon
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This study aims to deeply analyze the character of serial killers in Thomas Harris’ novels and focuses on his novel Red Dragon. The Study searches in these complex and deep characters through the use of Erich Fromm's concepts about the destructive nature of the human psyche and what are the factors affecting serial killers in all social psychological, and biological aspects. This study Concluded: Thomas Harris portrayed the characters of serial killers in a professional and complex and made the reader go on a contemplative journey in the mind and soul of the serial killer, thus reaching the climax of artistic perfection.

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Publication Date
Thu Jan 01 2015
Journal Name
Al–bahith Al–a'alami
Considerable use of computers and the Internet in managing public relations activities The Ministries of Justice and the Interior are examples
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She noted most of the results of research conducted on the use of computers and the Internet in the areas of administrative, economic, agricultural and educational to a significant improvement in learning outcomes of these groups in the development of mechanisms of action, has increased rates of computer use and applications in various spheres of life at very fast pace so that the computer and the Internet is a vital part of any activity, whether administrative or research or the media, hence it can be said that the use of computers and the Internet in the management of public relations activities in any organization can accelerate the pace of echo positive goals and purposes of public relations, this study comes to looking at us

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Publication Date
Mon Feb 01 2016
Journal Name
Al-academy
Calendar art activities in private schools Secondary School in Baghdad: سناء عبد الامير حسين
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The technical activities designed to highlight the creations of students by providing activities appropriate to their abilities and capabilities within and outside the school, which is a way for the development of learning and learner behavior aimed at directing guidance educationally and artistically.As a result of the efforts of modern educational activities, art has become part of the philosophy of the modern school and part of the modern curriculum. Because it is enough to configure the practices and habits of a satisfactory and acceptable, and is characterized by precision, order and beauty.Through the researcher with a survey of previous studies that dealt with art activities and found that all studies have been confined to a calen

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Publication Date
Tue Dec 13 2022
Journal Name
Dental Hypotheses
Comparative Evaluation of Marginal Microleakage Between Bulk-Fill, Preheated Bulk-Fill, and Bulk-Fill Flowable Composite Resins Above and Below Cemento-Enamel Junction Using Micro-Computed Tomography: An In Vitro Study
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Objective: The aim of this study was to compare the marginal microleakage between bulk-fill, preheated bulk-fill, and bulk-fill flowable composite resins above and below cemento-enamel junction (CEJ) using micro-computed tomography. Methods: Sixty freshly extracted premolar teeth were prepared with a slot shaped cavities of a total of 120 Class II: 3mm (bucco-lingual), 2mm (mesio-distal) with mesial-gingival margin located 1mm coronal to CEJ, and distal gingival margin located 1mm apical to the CEJ. The samples were randomly divided into two main groups according to the restorative material (Tetric EvoCeram and 3M Filtek), and each group was further sub-divided into three subgroups according to the consistency (bulk fill, preheated bulk fil

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