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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 Dec 15 2020
Journal Name
Al-academy
Novel Coronavirus Pandemic as it is Expressed by Children in Their Drawings On-line: An Analytical Study: نزار بن صالح أحمد عبد الحفيظ
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This study aimed at identifying how children express the emerging coronavirus in general and according to their age groups (4-13 years) by analyzing 91 of their drawings published online, using the descriptive content analytical approach. The results showed that children's artistic expression of the virus came according to the concepts and ideas they carried about the virus for the age groups of (4-7 years) and (7-9 years), while it came according to visual perception for age groups (9-11 years), and from (11-13) years. Also, most children were aware about the presence of the virus and its widespread around the world, but (99%) of them do not realize the seriousness of the virus. It was confirmed that between (25-34%) of children were su

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Publication Date
Wed Mar 10 2021
Journal Name
Baghdad Science Journal
The impact of concentrations of inorganic salts to compromise in rooting branches Genuine apples and apple architecture in vitro
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Took apple branches Genuine and Architecture tissue cultured in vitro 3 cm long and planted in the middle of food MS that contains different concentrations of inorganic salts and of Mntmat free growth and incubated Transplanter to study their effect on rooting Aalavra

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Publication Date
Thu Mar 30 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
In Vitro Effect of Cholesterol and Different Sugars on Digitonin Production in Multiplied Shoots of Digitalis purpurea L. Plant
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Production of  the steroidal saponin digitonin  in multiplied shoots of Digitalis purpurea , (var. Excelsior Mixed) has been achieved in vitro by two experiments. In the experiment 1, shoot tips ( 1cm length ) explants  from the sterilized seedlings were excised and cultured on MS medium ( Murashige and Skoog medium) supplemented with 0.5 mg/L TDZ (thidiazuron) and   cholesterol at the concentrations 0.0, 0.1, 0.3, 0.5, 1.0, 1.5, 2.0 or 4.0 mg/L. After 45 day, results showed that the treatment with 0.5 mg/L TDZ and 2.0mg/L cholesterol had a positive effected on increasing the dry weight of multiplied shoots and their production of digitonin when compared with other treatments, where this treatment gave 2

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Publication Date
Thu Jun 01 2023
Journal Name
Ifip Advances In Information And Communication Technology
Rapid Thrombogenesis Prediction in Covid-19 Patients Using Machine Learning
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Machine Learning (ML) algorithms are increasingly being utilized in the medical field to manage and diagnose diseases, leading to improved patient treatment and disease management. Several recent studies have found that Covid-19 patients have a higher incidence of blood clots, and understanding the pathological pathways that lead to blood clot formation (thrombogenesis) is critical. Current methods of reporting thrombogenesis-related fluid dynamic metrics for patient-specific anatomies are based on computational fluid dynamics (CFD) analysis, which can take weeks to months for a single patient. In this paper, we propose a ML-based method for rapid thrombogenesis prediction in the carotid artery of Covid-19 patients. Our proposed system aims

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Publication Date
Tue Dec 05 2023
Journal Name
Baghdad Science Journal
Synthesis and Antibacterial Evaluation for Some New Schiff-bases Derived from P-aminoacetanilide
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Derivatives of Schiff-bases possess a great importance in pharmaceutical chemistry. They can be used for synthesizing different types of bioactive compounds. In this paper, derivatives of new Schiff bases have been synthesized from several serial steps. The acid (I) was synthesized from the reaction of dichloroethanoic acid with 2 moles of p-aminoacetanilide. New acid (I) converted to its ester (II) via the reaction of (I) with dimethyl sulphate in the present of anhydrous of sodium carbonate and dry acetone. Acid hydrazide (III) has been synthesized by adding 80% of hydrazine hydrate  to the new ester using ethanol as a solvent. The last step included the preparation of new Schiff-bases (IV-VIII) by the reaction of acid hydrazide with

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Publication Date
Tue Dec 05 2023
Journal Name
Baghdad Science Journal
Synthesis and Antibacterial Evaluation for Some New Schiff-bases Derived from P-aminoacetanilide
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Derivatives of Schiff-bases possess a great importance in pharmaceutical chemistry. They can be used for synthesizing different types of bioactive compounds. In this paper, derivatives of new Schiff bases have been synthesized from several serial steps. The acid (I) was synthesized from the reaction of dichloroethanoic acid with 2 moles of p-aminoacetanilide. New acid (I) converted to its ester (II) via the reaction of (I) with dimethyl sulphate in the present of anhydrous of sodium carbonate and dry acetone. Acid hydrazide (III) has been synthesized by adding 80% of hydrazine hydrate  to the new ester using ethanol as a solvent. The last step included the preparation of new Schiff-bases (IV-VIII) by the reaction of acid hydrazide with app

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Publication Date
Sat Jul 01 2023
Journal Name
Indones. J. Ch Em
Synthesis, DFT Calculations, DNA Interaction, and Antimicrobial Studies of Some Mixed Ligand Complexes of Oxalic Acid and Schiff Base Trimethoprim with Various Metal Ions
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Mixed ligand metal complexes are synthesized from oxalic acid with Schiff base, and the Schiff base was obtained from trimethoprim and acetylacetone. The synthesized complexes were of the type [M(L1)(L2)], where the metal, M, is Ni(II), Cu(II), Cr(III), and Zn(II), L1 corresponds to the trimethoprim ((Z)-4-((4-amino-5-(3,4,5- trimethoxybenzyl)pyrimidine-2-yl)imino)pentane-2-one) as the first ligand and L2 represent the oxalate anion (𝐶􀬶𝑂􀬶 􀬶􀬿) as a second ligand. Characterization of the prepared compounds was performed by elemental analysis, molar conductivity, magnetic measurements, 1H-NMR, 13C-NMR, FT-IR, and Ultraviolet-visible (UV-Vis) spectral studies. The recorded infrared data is reinforced with density functional th

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Publication Date
Mon Aug 29 2022
Journal Name
Indonesian Journal Of Chemistry
Synthesis, DFT Calculations, DNA Interaction, and Antimicrobial Studies of Some Mixed Ligand Complexes of Oxalic Acid and Schiff Base Trimethoprim with Various Metal Ions
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Mixed ligand metal complexes are synthesized from oxalic acid with Schiff base, and the Schiff base was obtained from trimethoprim and acetylacetone. The synthesized complexes were of the type [M(L1)(L2)], where the metal, M, is Ni(II), Cu(II), Cr(III), and Zn(II), L1 corresponds to the trimethoprim ((Z)-4-((4-amino-5-(3,4,5-trimethoxybenzyl)pyrimidine-2-yl)imino)pentane-2-one) as the first ligand and L2 represent the oxalate anion ( ) as a second ligand. Characterization of the prepared compounds was performed by elemental analysis, molar conductivity, magnetic measurements, 1H-NMR, 13C-NMR, FT-IR, and Ultraviolet-visible (UV-Vis) spectral studies. The recorded infrared data is reinforced with density functional theory (DFT) calcul

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Publication Date
Tue Jan 21 2025
Journal Name
Applied Biochemistry And Biotechnology
Synthesis and characterization of new (Au, Ru, and Rh) ion complexes and evaluating their activity as anticancer and antioxidants
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Publication Date
Mon Dec 18 2017
Journal Name
Al-khwarizmi Engineering Journal
Optimization and Prediction of Process Parameters in SPIF that Affecting on Surface Quality Using Simulated Annealing Algorithm
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Incremental sheet metal forming is a modern technique of sheet metal forming in which a uniform sheet is locally deformed during the progressive action of a forming tool. The tool movement is governed by a CNC milling machine. The tool locally deforms by this way the sheet with pure deformation stretching. In SPIF process, the research is concentrate on the development of predict models for estimate the product quality. Using simulated annealing algorithm (SAA), Surface quality in SPIF has been modeled. In the development of this predictive model, spindle speed, feed rate and step depth have been considered as model parameters. Maximum peak height (Rz) and Arithmetic mean surface roughness (Ra) are used as response parameter to assess th

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