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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
Fri Sep 01 2023
Journal Name
Journal Of Molecular Structure
Synthesis, spectral studies, DFT, biological evaluation, molecular docking and dyeing performance of 1-(4-((2-amino-5-methoxy)diazenyl)phenyl) ethanone complexes with some metallic ions
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Four Co(II), (C1); Ni(II), (C2); Cu(II), (C3) and Zn(II), (C4) chelates have been synthesized with 1-(4-((2-amino- 5‑methoxy)diazenyl)phenyl)ethanone ligand (L). The produced compounds have been identified by using spectral studies, elemental analysis (C.H.N.O), conductivity and magnetic properties. The produced metal chelates were studied using molar ratio as well as sequences contrast types. Rate of concentration (1 ×10􀀀 4 - 3 ×10􀀀 4 Mol/L) sequence Beer’s law. Compound solutions have been noticed height molar absorptivity. The free of ligand and metal chelates had been applied as disperse dyes on cotton fabrics. Furthermore, the antibacterial activity of the produced compounds against various bacteria had been investigated. F

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Publication Date
Thu Feb 01 2018
Journal Name
Iosr Journal Of Pharmacy And Biological Sciences
Synthesis, Characterization of Organic Derivatives Containing Heterocyclic Rings and Evaluation Their Antibacterial Activity
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Schiff bases (Sh1-Sh3) have been synthesized (p-aminophenol) was condensed with different aromatic aldehyde in ethanol inthe presence of glacial acetic acid as catalyst. These Schiff bases on treatment with monochloroacetyl choride gave 3-chloro-1-(4-hydroxyphenyl)-4-(substituted)azetidin-2-one(Az4-Az6), with αmercaptoacetic acid gave 3-(4-hydroxyphenyl)-2-( substituted)thiazolidin-4-one (Th7-Th9) and with anthranilic acid gave 3-(4-hydroxyphenyl)-2(substituted)-2,3-dihydroquinazolin-4(1H)-one (Qu10-Qu12). The purity of the derivatives was confirmed by TLC. The some compoundsidentify by (FT-IR and1H, 13C-NMR) data. Some of derivatives were evaluated activity against several microbesto determine ability to inhibit bacterial in some h

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Publication Date
Tue Jun 20 2023
Journal Name
Baghdad Science Journal
Preparation, characterization, antioxidant activity of 1-(2-furoyl) thiourea derivatives and study the molecular docking of them as potent inhibitors of Urease enzyme
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In this work, we synthesized thirteen compounds of 1-(2-furoyl)thiourea derivatives 1-13 by conversion of 2-furoyl chloride to 2-furoyl isothiocyanate by reacting it with potassium thiocyanate in dry acetone in a quite short reflux time then, in the same pot, different of (primary and secondary amines) were added individually to achieve thiourea derivatives. The products were characterized spectroscopically using (FT-IR, 1H NMR and 13C NMR) techniques. Some of them were evaluated as antioxidant agents using DPPH radical scavenging method, and all were examined theoretically as enzyme inhibitors against Bacillus pasteurii urease (pdb id: 4ubp) and  by studying  molecular docking using Autodock (4.2.6) software.

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Publication Date
Wed Jun 26 2019
Journal Name
Research Journal Of Pharmaceutical, Biological And Chemical Sciences
Synthesis, Characterization Antimicrobial Activities Studies Of Mixed-Ligand Complexes Of Curcumin And Anthranilic Acid With Bivalent Metals Chlorides
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Publication Date
Fri Apr 01 2016
Journal Name
International Journal Of Chemical Engineering And Applications
Synthesis, Characterization, and Anti-microbial Study of Polycyclicacetal Metal Complexes Derived from PEG and (Erythro-Ascorbic Acid) Derivative
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Polymer metal complexes of poly ethylene glycol acetal and Ag (I), Cu (II), Ni (II), Mn (II), Co (III) and Hg (II) were prepared from the reaction of PEG with aldehyde derived from Erythro-ascorbic acid (pentulosono-ɣ-lactone-2, 3- enedianisoate). All these compounds were characterized by Thin Layer Chromatography (TLC) and FTIR spectra and aldehyde was also characterized by (U.V-Vis), 1HNMR,13CNMR, and mass spectra. It has been established that, the polymer and its metal complexes showed good activities against four pathogenic bacteria (Escherichia coli ,Klebsiellapneumonae, Staphylococcusaureus, Staphylococcus Albus) and two fungal (Aspergillus Niger,Yeast). The polymer metal complexes showed higher activity than the free polymer. The

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Publication Date
Wed Apr 20 2016
Journal Name
International Journal Of Chemical Engineering And Applications
Synthesis, Characterization, and Anti-microbial Study of Polycyclicacetal Metal Complexes Derived from PEG and (Erythro-Ascorbic Acid) Derivative
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Polymer metal complexes of poly ethylene glycol acetal and Ag (I), Cu (II), Ni (II), Mn (II), Co (III) and Hg (II) were prepared from the reaction of PEG with aldehyde derived fromErythro-ascorbic acid (pentulosono-ɣ-lactone-2, 3- enedianisoate). All these compounds were characterized by Thin Layer Chromatography (TLC) and FTIR spectra and aldehyde was also characterized by (U.V-Vis), 1HNMR,13CNMR, and mass spectra. It has been established that, the polymer and its metal complexes showedgood activities against four pathogenic bacteria (Escherichia coli , Klebsiellapneumonae,Staphylococcusaureus, Staphylococcus Albus) and two fungal (Aspergillus Niger,Yeast). The polymer metal complexes showed higher activity than the free polymer.Theorder

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Publication Date
Mon Jan 01 2024
Journal Name
Russian Journal Of Organic Chemistry
Synthesis and Biological Activity of Some New 1,3,4-Oxadiazoles Derived from Carboxylic Acids
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Publication Date
Thu Jul 01 2021
Journal Name
Chemical Methodologies
Novel Synthesis of Some N-Hydroxy Phthalimide Derivatives with Investigation of Its Corrosion Inhibition for Carbon Steel in HCl Solution
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In the current study, new derivatives were synthesized by reaction of N-hydroxyphthalimide with chloro acetyl chloride in the presence of Et3N as a base to form 1,3-dioxoisoindolin-2-yl 2-chloroacetate (B1), which in turn enters several reactions with different amines where it interacts with primary amines to give 1,3-dioxoisoindolin-2-yl acetate derivatives (B2-B4) in basic medium, in the same way it interacts with these amines but with adding KNCS to form thiourea derivatives (B5-B7). It also reacts with diamines to give bis(azanediyl) derivatives (compounds B8-B10). The prepared derivatives were diagnosed using infrared FTIR and 1HNMR,13CNMR for some derivatives. Compounds B4, B5 and B9 were measured as corrosion inhibitors the inhibitio

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Publication Date
Sun Mar 10 2013
Journal Name
Journal Of Life Sciences And Technologies
Synthesis, Characterization, and Anti-Microbial Study of Metal Complexes of Polycyclicacetal derived from PVA & Erythro-Ascorbic acid derivative
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The aim of this work is the synthesis of new grafted PVA polymer with a derivative of Erythro-ascorbic acid (pentulosono-ɣ -lactone-2, 3-enedianisoate). All synthesized compounds were characterized by thin layer chromatography (TLC) and FTIR spectra and aldehyde was also characterized by (U.V-Vis), 1HNMR, 13CNMR and mass spectra. They were also evaluated for antimicrobial properties by dilute method against four pathogenic bacteria (Escherichia coli ,Klebsiella pneumonae, Staphylococcus aureus, Staphylococcus Albus) and two fungal (Aspergillus Niger, Yeast). All polymer metal complexes showed good activities against the various microbial isolates. The polymer metal complexes showed higher activity than the free polymer. The order of increa

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Publication Date
Thu Mar 01 2018
Journal Name
International Journal Of Science And Nature
EXPERIMENTAL AND THEORETICAL STUDY OF 3-BENZYL -2- MERCAPTOQUINOIZOLINE-4(3H)-ONE (BMQ) AS AN INHIBITOR OF CARBON STEEL CORROSION IN ACIDIC MEDIA
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The inhibition of 3-Benzyl -2-mercaptoquinoizoline -4 (3H)-one (BMQ) on the corrosion of carbon steel in 0.5 M HCl studied by potentionstat polarization methods at 303–333 K. Results obtained show that BMQ act as inhibitor for carbon steel in HCl solution. The inhibition efficiency increase with increase in BMQ concentration. Activation parameters and Gibbs free energy for the adsorption process using Statistical Physics calculated and discussed. Quantum chemical calculations using DFT at the B3LYP/6-31G level of theory were used to calculate some electronic properties of the molecule to verify any correlation between the inhibitive effect and molecular structure of BMQ. The quantum calculations were proceeded to get data around correlati

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