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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
Sun Jan 15 2012
Journal Name
Talanta
Molecularly imprinted polymer as sorbent in micro-solid phase extraction of ochratoxin A in coffee, grape juice and urine
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A simple, environmental friendly and selective sample preparation technique employing porous membrane protected micro-solid phase extraction (μ-SPE) loaded with molecularly imprinted polymer (MIP) for the determination of ochratoxin A (OTA) is described. After the extraction, the analyte was desorbed using ultrasonication and was analyzed using high performance liquid chromatography. Under the optimized conditions, the detection limits of OTA for coffee, grape juice and urine were 0.06 ng g−1, 0.02 and 0.02 ng mL−1, respectively while the quantification limits were 0.19 ng g−1, 0.06 and 0.08 ng mL−1, respectively. The recoveries of OTA from coffee spiked at 1, 25 and 50 ng g−1, grape juice and urine samples at 1, 25 and 50 ng mL

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Publication Date
Tue Dec 01 2015
Journal Name
Journal Of Engineering
Civilizations and Environmental Particulars of Place in Islamic Holy Thresholds in Iraq (Alkadhumain Holy Threshold as a case study)
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Islamic shrines architecture is one of the Islamic Architectural building types. It is called (Thresholds); (Atabat) in Arabic. Thoroughbred throughout the Islamic world from the east to west. In addition, it carries the style features and peculiarities of uniqueness from the rest of the types of Islamic architecture. By virtue of the particularity of its function as tomb for important person in Islamic history. Islamic shrines architecture has grown and evolved in started from the small shrines, and then taken to widen with the evolution of time in line with the value of the event and the rituals associated with it. Some of them to became centers of large cities of the largest in many parts of the Islamic world.

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Publication Date
Wed Oct 29 2025
Journal Name
The Indonesian Biomedical Journal
Genotype Combination of rs1042044 and rs6458093 in GLP-1R as A Genetic Risk for Osteoporosis in Postmenopausal Iraqi Women
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BACKGROUND: Many genetic factors are known to be related to osteoporosis, and currently the role of the glucagon-like peptide-1 receptor (GLP-1R) gene in bone health has been studied intensively. Some variation of this gene, such as rs1042044 and rs6458093, are known to be linked to metabolic diseases and lower bone mineral density, however their specific contribution to osteoporosis remains largely unexplored. Therefore, this study was conducted to investigate the combined genotypic effect of rs1042044 and rs6458093 as a genetic risk factor for osteoporosis in postmenopausal Iraqi women.METHODS: Blood samples from 75 osteoporosis patients and 75 healthy controls, aged 45-85, were collected. DNA was extracted, and a region of GLP-1R

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Publication Date
Mon Jan 01 2024
Journal Name
Oral Health And Preventive Dentistry
Antioxidant and Antineoplastic Activities of Hibiscus sabdariffa Linn. Petal Extracts against Oral Squamous Cell Carcinoma Cell Line
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Purpose: To assess the antioxidant and antineoplastic effects of Hibiscus sabdariffa Linn. on oral squamous cell carcinoma cells. Materials and Methods: Human squamous cell carcinoma HSCC cells were tested for cytotoxicity by a methanol extract of Hibiscus sabdariffa (MEHSP). After 24, 48, and 72 ...

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Publication Date
Sat Mar 08 2025
Journal Name
Chemistry Africa
Preparation, Characterisation, and Photochemical Stability of Polymeric Derivatives of Polyvinyl Alcohol Grafted with Phthalic Anhydride and Dyes
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In this study, derivatives of polyvinyl alcohol (PVA) grafted with phthalic anhydride (PhA) and dyes were prepared to produce polymeric materials of PVA-g-PhA, PVA-g-PhA-anthocyanin, PVA-g-PhA-bromophenol blue, and PVA-g-PhAthymol blue. The materials were characterised by FTIR and 1 H NMR spectroscopies. The crystallinity of the polymers was evaluated with powder X-ray difraction, and the thermal stability by thermogravimetric analysis (TGA). The synthetic procedure for the polymeric materials entailed the formation of esters. The FTIR spectra of the polymers confrmed their formation since the ester carbonyl group stretch was observed at approximately 1691–1716  cm−1 in each material. NMR spectroscopy confrmed the addition of t

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Publication Date
Thu Dec 08 2011
Journal Name
مجلة الاداب
Morphophonemic Awareness of English Derivatives by Iraqi College Students
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MR Younus, Al-A'DAB, 2011

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Publication Date
Mon Mar 08 2021
Journal Name
Baghdad Science Journal
Charge Transfer studies of some oxadiazole derivatives with different
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the physical paraneters of oxadizole derivaties as donor molecules have been measured the charge transfer and methanol as solvent have been estimated from the electonic spectra

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Publication Date
Sat Nov 15 2025
Journal Name
Baghdad Science Journal
Synthesis, Characterization and Biological Activity Studies of New Metal Ion Complexes With Schiff Base Derived from (Z)-3-Hydrazineylidene-1-Phenylpyrazolidine and Evaluating Them as Antioxidants
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Publication Date
Sun Jan 01 2017
Journal Name
Iraqi Journal Of Agricultural Sciences 47 (1)‏
Effect of irrigation intervals and foliar of salicylic acid on growth and yield of Potato
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Publication Date
Tue Dec 31 2019
Journal Name
Research On Crops
Influence of foliar application of ascorbic acid and atonik on growth and yield of potato
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