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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
Tue Jan 01 2019
Journal Name
Asian Journal Of Chemistry
Synthesis, Characterization and Microbial Evaluation of Heterocyclic Azo Dye Ligand Complexes of Some Transition Metal(II) Ions
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The snthesis and characterization of cobalt(II), nickel(II), copper(II) and zinc(II) complexes of azo ligand 4-[(5-acetyl-2-aminophenyl)- diazenyl]-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one derived from 4-aminoantipyrine and 4-aminoacetophenone are reported. The nature of the compounds have been studied followed by mole ratio and methods of continuous contrast, Beer′s law followed during a condensation rate (1 × 10-4 – 3 × 10-4 M). The analytical data showed that all the complexes are in 1:2 metal-ligand ratio. An octahedral geometry have been suggested for all the compounds and biological studies of all the complexes were evaluated against different types of antimicrobial strains.

Publication Date
Fri Jan 15 2021
Journal Name
Psychology And Education Journal
Property and Possession in Gayl Jones’s Novel Corregidora: A Study in African American Literature and Literary Theory
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the traumatic memory of their ancestors. The novel navigates sites of trauma, memory, and blues music while resisting the bourgeoisie-capitalist relationships that permeated not only white society but also African American communities. Jones’s novel presents the plight of an African American woman, Ursa, caught between the memory of her enslaved foremothers and her life in an emancipated world. The physical and spiritual exploitation of African American women who bear witness to the history of slavery in Corregidora materializes black women’s individuality. This article is framed by trauma studies as well as the Marxists’ concepts of commodification, accumulation, and production. Ursa, one of the Corregidora women, represents

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Publication Date
Sun Oct 22 2023
Journal Name
Iraqi Journal Of Science
Brain Tumor Detection of Skull Stripped MR Images Utilizing Clustering and Region Growing
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Brain tissues segmentation is usually concerned with the delineation of three types of brain matters Grey Matter (GM), White Matter (WM) and Cerebrospinal Fluid (CSF). Because most brain structures are anatomically defined by boundaries of these tissue classes, accurate segmentation of brain tissues into one of these categories is an important step in quantitative morphological study of the brain. As well as the abnormalities regions like tumors are needed to be delineated. The extra-cortical voxels in MR brain images are often removed in order to facilitate accurate analysis of cortical structures. Brain extraction is necessary to avoid the misclassifications of surrounding tissues, skull and scalp as WM, GM or tumor when implementing s

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Publication Date
Tue Feb 28 2023
Journal Name
Iraqi Journal Of Science
Mixed Spinel Co0.4Zn0.6Fe2O4 Ferrite Nanoparticles As a Magnetic Photocatalyst: Synthesis and Dye Degradation
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        In this paper, mixed spinel Co0.4Zn0.6Fe2O4 ferrite was synthesized by microwave-assisted combustion method. Photocatalytic activity of the as-synthesized sample was investigated against methylene blue dye at room temperature at different exposure times (60-360 min.) under visible light. Phase impurity and surface morphology which are investigated with XRD analysis and field emission- scanning electron microscopy, indicate that a cubic spinel unit cell structure with a crystilite size and lattice constant are 22.5048nm and 8.37Å, respectively. The saturation magnetization exhibited directly from the hysteresis loop is (70.20emu/g). Optical properties for the investigated ferrite

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Publication Date
Mon Jan 01 2024
Journal Name
Journal Of Applied Pharmaceutical Science
The role of angiotensin converting enzyme (insertion)/(deletion) and angiotensin II type 1 receptor (A1166C) gene polymorphisms in antiproteinuric effect of ACE inhibitors in type 2 diabetic Iraqi patients
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The angiotensin converting enzyme (ACE) I\D gene polymorphism influences the blood ACE enzyme activity. Renoprotective effect of ACE inhibitors (ACEIs) varies among patients due to genetic variation, particularly in Renin-Angiotensin-Aldosterone System genes. This study investigates the genetic variations of ACE I\D and AGT1RA1166C gene polymorphisms in the antiproteinuric effect of ACEI therapy in type 2 diabetes mellitus (T2DM) patients. This is a cross-sectional study that included 76 T2DM patients who are ACEI users, divided into two groups: T2DM without diabetic kidney disease (DKD) included 31 patients, and T2DM with DKD included 45 patients. Urine samples were taken for measurement of urine albumin and creatinine, then calcul

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Publication Date
Sun Oct 01 2023
Journal Name
Baghdad Science Journal
Green synthesis of CdS:Sn NPs by Starch as a Covering Agent and Studying its Physical Properties
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The aim of this research is to employ starch as a stabilizing and reducing agent in the production of CdS nanoparticles with less environmental risk, easy scaling, stability, economical feasibility, and suitability for large-scale production. Nanoparticles of CdS have been successfully produced by employing starch as a reducing agent in a simple green synthesis technique and then doped with Sn in certain proportions (1%, 2%, 3%, 4%, and 5%).According to the XRD data, the samples were crystallized in a hexagonal pattern, because the average crystal size of pure CdS is 5.6nm and fluctuates in response to the changes in doping concentration 1, 2, 3, 4, 5 %wt Sn, to become   4.8, 3.9, 11.5, 13.1, 9.3 nm respectively. An increase in crystal

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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
Mon Jan 01 2024
Journal Name
Cytokine
Evaluation of IL-8, nitric oxide and macrophage inhibitory factor as clinical circulatory markers in patients with cutaneous leishmaniasis, before and during sodium stibogluconate treatment
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The clinical spectrum of cutaneous leishmaniasis (CL), an intracellular parasitic pathogen, ranges from a single sore healing to chronic crusty lesions with a manifestation of treatment resistance. The complicated interaction between Leishmania bodies and the early immune response, including innate and adaptive mechanisms, determines the evolution of nodules. This study examined the levels of the chemoattractant interleukin 8 (IL-8), pro-inflammatory nitric oxide (NO), and immunoregulatory macrophage inhibitory factor (MIF) in the serum of subjects recently diagnosed with cutaneous leishmaniasis, in parallel with patients being monitored during consecutive sodium stibogluconate (Pentostam) treatment. A total of 161 serum samples of newly di

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Publication Date
Sun May 21 2017
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
Antimicrobial Activities of Aqueous and Methanolic Extracts from Salvia officinalis and Salix acmophylla Used in the treatment of wound infection isolates
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    The aqueous and methanol extracts of Salvia officinals and Salix acmoplylla traditionally used for the treatment of infections disease were tested for their active  against gram positive and gram negative bacteria isolated from wound  infection culture using the broth dilution and disc diffusion melhod. Results of   this study revealed the prescence of phytochemical which were  active  against gram positive and negative bacteria. Methanol extracts of both plants showed  the highest activity other the aqueous extract. The minimum inhibitory concentration (MIC) of the aqueous extracts on the test organism was  25- 100 mg\ml,while that of the  methanol extract was ranged betwee

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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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