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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 Mar 31 2022
Journal Name
Journal Of The College Of Education For Women
News of Zubarah Family- Unionists in Nishapur and their Scientific Contributions in the two Centuries (4-6 AH/10-12 AD)
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This research is concerned with qualitatively studying the history of an ancient family, one of the most prominent noble, Alawite families, that assumed the position of the Student Union for the Alawite Supervision in the city of Nishapur in Khorasan during the centries (4-6 H./ 10-12 A.H.). Thus, the research aims to investgate the historical news, and the outstanding Zubarah figures who experience the supereme the religious, historical and scientific position in Khorasan generally and Nishapur particularily. It further aims at arriving at the true meaning of the name Zubarah, and to whom it was called, and the extent of this family’s affiliation to the noble Alawi House, and how they moved to live and settle in the cities of the East

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Publication Date
Mon Oct 14 2019
Journal Name
Applied Sciences
Synthesis of Novel Heteroatom-Doped Porous-Organic Polymers as Environmentally Efficient Media for Carbon Dioxide Storage
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The high carbon dioxide emission levels due to the increased consumption of fossil fuels has led to various environmental problems. Efficient strategies for the capture and storage of greenhouse gases, such as carbon dioxide are crucial in reducing their concentrations in the environment. Considering this, herein, three novel heteroatom-doped porous-organic polymers (POPs) containing phosphate units were synthesized in high yields from the coupling reactions of phosphate esters and 1,4-diaminobenzene (three mole equivalents) in boiling ethanol using a simple, efficient, and general procedure. The structures and physicochemical properties of the synthesized POPs were established using various techniques. Field emission scanning elect

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Publication Date
Sun May 14 2017
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
A Complete (k,r)-Cap in PG(3,p) Over Galois Field GF(4)
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   The aim of this paper is to construct the (k,r)-caps in the projective 3-space PG(3,p) over Galois field GF(4). We found that the maximum complete (k,2)-cap which is called an                       ovaloid  , exists in PG(3,4) when k = 13. Moreover the maximum (k,3)-caps, (k,4)-caps and   (k,5)-caps. 

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Publication Date
Sun Jun 05 2016
Journal Name
Baghdad Science Journal
Biodegradation Studies in Vitro of Novel Poly(adipic anhydride-co-mannitol)-N-maleoyl Chitosan Networks
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In this work, novel copolymers of poly(adipic anhydride-co-mannitol) were synthesized by melting condensation polymerization of poly(adipic anhydride) with five percentages of mannitol sugar, 1 to 5 Wt.%. These copolymers were purified and then, characterized by FT-IR, which was proved that the cross-linking reaction was caused by nucleophilic attack of mannitol hydroxyl group to acidic anhydride groups of poly(adipic anhydride) backbone and new ester groups were formed and appeared. Also, modified organic-soluble chitosan, N-maleoyl-chitosan, were synthesized by grafting reaction of chitosan with maleic anhydride in DMF as solvent, and it was also purified and characterized by FT-IR. Biodegradation in vitro of the IPNs of poly(adipic anhyd

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Publication Date
Thu Jun 01 2023
Journal Name
Materials Chemistry And Physics
In-vitro antibacterial, cytotoxicity, and anti-prostate cancer effects of gold nanoparticles synthesized using extract of desert truffles (Tirmania nivea)
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Herein, a cost-effective bio approach using extract derived from desert truffles (Tirmania nivea) is utilized to synthesize gold nanoparticles (AuNPs). AuNPs were thoroughly investigated using UV–vis, XRD, SEM, and TEM analyses. It was shown that nanoparticles had an fcc structure with a smooth spherical surface, an average diameter of 9.44 ± 0.26 nm, and an SPR band observed at 548 nm. Investigations were conducted on AuNPs' antibacterial and anti-cancer properties of prostate cancer cells. The findings suggest that AuNPs showed better antibacterial effects against S. aureus compared to E. coli, P. aeruginosa, and K. pneumoniae. AuNPs’ combination with antibiotics demonstrated a synergistic effect with significant antibacterial activi

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Publication Date
Sat Oct 28 2023
Journal Name
Baghdad Science Journal
Small Nuclear RNA 64 (snoRNA64): A novel Tumor Biomarker for Pancreatic Cancer
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The pancreatic ductal adenocarcinoma (PDAC), which represents over 90% of pancreatic cancer cases,
has the highest proliferative and metastatic rate in comparison to other pancreatic cancer compartments. This
study is designed to determine whether small nucleolar RNA, H/ACA box 64 (snoRNA64) is associated with
pancreatic cancer initiation and progression. Gene expression data from the Gene Expression Omnibus (GEO)
repository have shown that snoRNA64 expression is reduced in primary and metastatic pancreatic cancer as
compared to normal tissues based on statistical analysis of the in Silico analysis. Using qPCR techniques,
pancreatic cancer cell lines include PK-1, PK-8, PK-4, and Mia PaCa-2 with differ

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Publication Date
Sun Jun 02 2013
Journal Name
Baghdad Science Journal
Synthesis of New Pyrazoline - Phenoxathiin Derivatives
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Phenoxathiin was prepared by the reaction of diphenyl ether with sulfur in the presence of anhydrous aluminum chloride. This work comprised the synthesis of new phenoxathiin derivatives containing heterocyclic moieties. These heterocyclic compounds were synthesized in three groups. The first group was made up of 2-(oxoalken-1-yl) phenoxathiin derivatives (3a-3j) obtained from the reaction of 2-acetylphenoxathiin with different aromatic aldehyde in the presence of sodium hydroxide. The other two groups involved compounds produced from the reaction of (3a-3j) with hydrazine hydrate in acetic acid to get 2-(1-acetyl pyrazolin-3-yl) phenoxathiin derivatives (4a-4j), and phenyl hydrazine in the presence of piperidine to afford 2-(1-phenyl pyrazo

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Publication Date
Wed Jan 14 2009
Journal Name
Diala , Jour
Synthesis of Barbiturate Derivatives from Imines
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Publication Date
Wed Sep 12 2018
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
Two Derivative Spectrophotometric Methods for the Simultaneous Determination of 4-AminoAntipyrine in Presence of Its Acidic Products
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Simple, economic and sensitive mathematical spectrophotometric methods were developed for the estimation 4-aminoantipyrine in presence of its acidic product. The estimation of binary mixture 4-aminoantipyrine and its acidic product was achieved by first derivative and second derivative spectrophotometric methods by applying zero-crossing at (valley 255.9nm and 234.5nm) for 4-aminoantipyrine and (peak 243.3 nm and 227.3nm) for acidic product. The value of coefficient of determination for the liner graphs were not less than 0.996 and the recovery percentage were found to be in the range from 96.555 to 102.160. Normal ratio spectrophotometric method 0DD was used 50 mg/l acidic product as a divisor and then measured at 299.9 nm with correlat

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Publication Date
Thu May 17 2018
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
Two Derivative Spectrophotometric Methods for the Simultaneous Determination of 4-AminoAntipyrine in Presence of Its Acidic Products
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    Simple, economic and sensitive mathematical spectrophotometric methods were developed for the estimation 4-aminoantipyrine in presence of its acidic product. The estimation of binary mixture 4-aminoantipyrine and its acidic product was achieved by first derivative and second derivative spectrophotometric methods by applying zero-crossing at (valley 255.9nm and 234.5nm) for 4-aminoantipyrine and (peak 243.3 nm and 227.3nm) for acidic product. The value of  coefficient of determination  for the liner  graphs were  not less than 0.996 and the recovery percentage were found to be in the range from 96.555 to 102.160. Normal ratio spectrophotometric method 0DD was used 50 mg/l acidic product as a divisor

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