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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 01 2006
Journal Name
Acta Crystallographica Section E
(OC-6-32)-Bis[5-bromo-2-(4-bromophenyldiazenyl) phenyl]dicarbonylruthenium(II)
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The title compound, [Ru(C12H7Br2N2)2(CO)2], possesses a distorted octahedral environment about the Ru atom, with two cyclometallated 4,40-dibromoazobenzene ligands and two mutually cis carbonyl ligands. The donor atoms are arranged such that the N atoms are respectively trans to a carbonyl ligand and an aryl C atom. Comment The title compound, (I), has been prepared as a minor product of the reaction of Ru3(CO)12 and 4,40-dibromoazobenzene in refluxing n-octane; the major product is the cluster complex Ru3(3-NC6H4Br)2(CO)9 (Willis et al., 2005). Two strong (CO) absorptions at 2039 and 1991 cm1 in the IR spectrum of (I) are consistent with the presence of two mutually cis carbonyl groups. The crystal structure was investigated to ascertai

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Publication Date
Sun Sep 22 2019
Journal Name
Baghdad Science Journal
Synthesis and Characterization of New Selenonitrone Derivative and Its Effect on Breast Cancer Cell Line Viability in Vitro
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          New nitrone and selenonitrone compounds were synthesized. The condensation method between N-(2-hydroxyethyl) hydroxylamine and substituted carbonyl compounds such as [benzil, 4, 4́-dichlorobenzil and  2,2́ -dinitrobenzil] afforded a variety of new nitrone compounds while the condensation between N-benzylhydroxylamine and substituted selenocarbonyl compounds such as [di(4-fluorobenzoyl) diselenide and (4-chlorobenzoyl selenonitrile] obtained selenonitrone compounds. The condensation of N-4-chlorophenylhydroxylamine with dibenzoyl diselenide obtained another type of selenonitrone compounds. The structures of the synthesized compounds were assigned based on spectroscopic data (FT-IR,

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Publication Date
Sun Dec 18 2022
Journal Name
Journal Of The College Of Basic Education
A (k,ℓ) Span in Three Dimensional Projective Space PG(3,p) Over Galois Field where p=4
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الغرض من هذا العمل هو دراسة الفضاء الإسقاطي ثلاثي الأبعاد PG (3، P) حيث p = 4 باستخدام المعادلات الجبرية وجدنا النقاط والخطوط والمستويات وفي هذا الفضاء نبني (k، ℓ) -span وهي مجموعة من خطوط k لا يتقاطع اثنان منها. نثبت أن الحد الأقصى للكمال (k، ℓ) -span في PG (3،4) هو (17، ℓ) -span ، وهو ما يساوي جميع نقاط المساحة التي تسمى السبريد.

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Publication Date
Wed Jan 01 2003
Journal Name
Ibn Al-haitham . J . For Pure & Appl Sci
Synthesis and characterization of new orttho - amino phenyl thio derivatives and their complexes
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Two ligand ortho-amino phenyl thio benzyl (L1) and 1,3 bis (ortho - amino phenyl thio ) acetone (L2) and their complexes have been prepared and characterized . The L1 ligand is lossing phenyl group on complexcation and forming 1,2 bis (ortho - amino phenyl thio ) ethane L3 and this tetrahedrally coordinated to the metal ion ( M+2 = Ni , Cu , Cd ) and octahedrally coordinated with mercury and cobalt ions , while the ligand L2 is behave as tridentate ligand forming octahedrally around chrome metal ion . Structural , diagnosis were established by i.r , Uv- visible , conductivity elemental analysis and (mass spectra , H nmr spectra for( L1 , L2 ) .

Publication Date
Sat Apr 01 2023
Journal Name
Russian Journal Of General Chemistry
Synthesis and Characterization of Metals Complexes with Uracil and Uracil Derivatives (A Review)
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Publication Date
Sat Nov 04 2023
Journal Name
Russian Journal Of General Chemistry
Synthesis and Characterization of Metals Complexes with Uracil and Uracil Derivatives (A Review)
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Previous studies on the synthesis and characterization of metal chelates with uracil by elemental analysis, conductivity, IR, UV-Vis, NMR spectroscopy, and thermal analysis were covered in this review article. Reviewing these studies, we found that uracil can be coordinated through the electron pair on the N1, N3, O2, or O4 atoms. If the uracil was a mono-dentate ligand, it will be coordinated by one of the following atoms: N1, N3 or O2. But if the uracil was bi-dentate ligand, it will be coordinated by atoms N1 and O2, N3 and O2 or N3 and O4. However, when uracil forms complexes in the form of polymers, coordination occurs through the following atoms: N1 and N3 or N1 and O4.

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Publication Date
Tue Nov 01 2022
Journal Name
Chemical Methodologies
Synthesis and Characterization of New Substituted Coumarin Derivatives and Study Their Biological Activity
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New substituted coumarins derivatives were synthesized by using nitration reaction to produce different nitro coumarin isomers which were separated from these isomers by using different solvent, and the reduction of nitro compounds was done to give corresponding amino coumarins. Temperature and reaction time of reaction were very important factors in determining the most productive nitro isotopes. A low temperature for three hours was sufficient to give a high product of a compound 6-nitro coumarin while increasing the temperature for a period of twenty-four hours that gave a high product of 8-nitro-coumarin. The synthesized compounds were confirmed by FT-IR,1 H-NMR, and13 C-NMR spectroscopy and all final compounds were tested for their ant

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Publication Date
Sun Jun 26 2022
Journal Name
International Journal Of Corrosion And Scale Inhibition
Theoretical and experimental studies of copper(II) and nickel(II) complexes derived from the ligand N-benzyl benzimidazole as corrosion inhibitors in ionic and bacterial media
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Publication Date
Mon Jun 03 2024
Journal Name
Journal Of Kufa For Chemical Sciences
Synthesis and Preliminary Biological study of New Chalcone Derivatives Containing Isoxazoline Moiety
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                          In this research work, synthesis, antimicrobial and antioxidant bioactivity of a chain of compounds having unsaturated ketones bond and isoxazoline moiety have been described. New chalcone derivatives containing isoxazoline moiety have been synthesized. Generally, Chalcones are unsaturated ketones bearing (-CO-CH=CH-) as reactive ketoethylenic group that give the bright yellow colored compounds due to this chromophore group.  Firstly, chalcones (IIa-d) have been prepared by cyclocondensation (Claisen-Schmidt condensation) of triphenyl aminobenzaldehyde with different substituted acetophenone in ethyl alcohol to produce a series of chalcones compounds with bright yellow colored as a

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Publication Date
Mon Mar 20 2023
Journal Name
Liquid Crystals
Synthesis and study the mesomorphic behaviour of some new 1,3,4-thiadiazoline derivatives
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Investigation of mesomorphic properties of new 1,3,4-thiadiazolines (which are synthesised via many steps in Scheme 1) was carried out in this study. These compounds are designed to have a heterocyclic unit, a carboxylate linkage group and a polar ether chain at the end of the molecule adjacent to the benzene ring, which enhance the dipolar interactions forces (varied from one to eight carbons) to investigate the association properties of their phases. The structure of the target compounds and the intermediates were confirmed by 1H NMR, 13C NMR, mass and FTIR spectral techniques. Polarised microscopic studies revealed that all the compounds in the series exhibited enantiotropic liquid crystalline properties. This was further confirmed using

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