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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 Dec 09 2018
Journal Name
Baghdad Science Journal
Synthesis, Characterization of Poly Heterocyclic Compounds, and Effect on Cancer Cell (Hep-2) In vitro.
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A synthesis series of new heterocyclic derivatives (A2-A7) (pyrrole, pyridazine, oxazine and imidazol) derived from 4-acetyl-2,5-dichloro-1-(3,5-dinitrophenyl)-1H-pyrrole-3-carboxylate(A1) have been synthesised. Synthesis of compound (A2) by the reaction of starting material (A1) with hydroxyl amine hydrochloride in the presence of pyridine. Compound (A2) was reacted with hydrazine hydrate in dry benzene to give (A3) derivative. The compound )A3( deals with sodium nitrite to give diazonium salt, and the reaction diazonium salt with ethyl acetoacetate to produce compound (A4). To a mixture of compound (A4) and hydroxyl amine with sttired to yield (A5).Compound (A6) was prepared by reaction compound (A4) with thiosemicarbazide in presence

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Publication Date
Wed Mar 15 2023
Journal Name
Journal Of Baghdad College Of Dentistry
Effect of a novel coating material on the microleakage of glass hybrid restoration in primary teeth – An in vitro study
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Background: Glass ionomer restorations are widely employed in the field of pediatric dentistry. There is a constant demand for a durable restoration that remains functional until exfoliation. This study aimed to measure and compare the effect of a novel coating material (EQUIA Forte Coat) on the microleakage of glass hybrid restoration (EQUIA Forte HT) in primary teeth. Material and method: Thirty cavitated (class-II) primary molars were allocated randomly into two groups based on the coat application; uncoated (control) and coated group (experimental). Cavities were prepared by the use of a ceramic bur (CeraBur) and restored with EQUIA Forte HT with or without applying a protective coat (EQUIA Forte Coat). Samples went through the

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Publication Date
Wed Mar 15 2023
Journal Name
Journal Of Baghdad College Of Dentistry
Effect of a novel coating material on the microleakage of glass hybrid restoration in primary teeth – An in vitro study
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Background: Glass ionomer restorations are widely employed in the field of pediatric dentistry. There is a constant demand for a durable restoration that remains functional until exfoliation. This study aimed to measure and compare the effect of a novel coating material (EQUIA Forte Coat) on the microleakage of glass hybrid restoration (EQUIA Forte HT) in primary teeth. Material and method: Thirty cavitated (class-II) primary molars were allocated randomly into two groups based on the coat application; uncoated (control) and coated group (experimental). Cavities were prepared by the use of a ceramic bur (CeraBur) and restored with EQUIA Forte HT with or without applying a protective coat (EQUIA Forte Coat). Samples went through the therm

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Publication Date
Wed Jun 21 2017
Journal Name
Research Journal Of Pharmaceutical, Biological And Chemical Sciences
Synthesis and characterization of Mixed-Ligand Complexes of Oxalic Acid and Trimethoprim with Mn(II), Co(II), Ni(II), Cu(II),Zn(II), and Cr (III) Ions: and antimicrobial Activities
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Publication Date
Thu May 21 2026
Journal Name
Journal Of Baghdad College Of Dentistry
In Vitro Evaluation of Shear Bond Strength of Sapphire Brackets after Dental Bleaching
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Background: The present study was conducted to evaluate the effects of different bleaching methods on the shear bond strength of orthodontic Sapphire brackets bonded to human premolars teeth using light cured composite resin and to determine the predominant site of bond failure. Materials and Methods: Thirty freshly extracted human premolars were selected and randomly divided into three groups (10 per group). These groups are: control (unbleached) group, hydrogen peroxide group (HP) 37.5% ; which is the in- office bleaching method group, carbamide peroxide group (CP) 16%; which is the at- home bleaching method group. After bleaching process was performed, all the teeth stored in distilled water in a sealed container at room temperature for

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Publication Date
Thu Jun 29 2023
Journal Name
Farmacia
CORRELATION BETWEEN INTEGRIN ALPHA-4 GENE POLYMORPHISMS AND FAILURE TO RESPOND TO NATALIZUMAB THERAPY IN IRAQI MULTIPLE SCLEROSIS PATIENTS
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Publication Date
Sat Jul 01 2023
Journal Name
Journal Of Physics: Conference Series
Mixed Ligand Complexes of Schiff Base and Nicotinamide: Synthesis, Characterization and Antimicrobial Activities
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A new Schiff base of HL has been synthesized from amoxicillin drug and 4- Chlorobenzophenone. Cr (III), Fe (III), Co (II), Ni (II), Cu (II), Cd (II) and Hg (II) mixed ligands complexes of Schiff base and Nicotinamide. Diagnosis of synthesis ligand and its complexes are done by 1HNMR, 13CNMR and thermal analysis for HL ligand, FTIR, UV-visible, molar conductance, CHN analysis, magnetic susceptility and atomic absorption. Octahedral geometries have been suggested for all complexes. All compounds under study were tested antimicrobial activity against four type of bacteria such as Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus Bacillis subtilis in nutrient agar.

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Scopus
Publication Date
Tue Dec 01 2015
Journal Name
Journal Of Al-nahrain University-science
Synthesis of Polyacrylamides from Derivatives 2-Aminobenzothiazole and also Preparation of Dibutylphthalate as a Plasticizer to Estimate Plasticization Behaviour for Prepared Polymers
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Publication Date
Mon Mar 27 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Synthesis and Antibacterial Activity of bis Heterocyclic Derivatives of 1,3,4-thiadiazole
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The Chemistry of heterocyclic sulphur and nitrogen containing compounds have a great role in the  field of scientific studies, The 2-amino 5-mercapto-1,3,4-thiadiazole ring for instance, has gained more importance in recent years because  they are considered as potent biologically active nucleus. In this study disulfide derivative can be obtained by oxidation with hydrogen peroxide of thiol group of the heterocyclic 2-amino 5-mercapto-1,3,4-thiadiazole ring to obtain compound (3) with expected antibacterial  activity. In order to use it as a diazo component to prepare some new bis azo compounds as possible antibacterial  agents, the reaction of two primary amino groups on both sides of disulfide dimer with sodium nitr

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Publication Date
Sun Dec 30 2018
Journal Name
Baghdad Science Journal
Synthesis and study of biological activity of some new Imidazole derivatives
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In this work ester derivatives were synthesized by the reaction of imidazole derivatives (C1) with ethylchloroacetate in ethanol and NaOH to give the corresponding (C2) .While compound (C3) acetohydrazide was synthesized by the reaction of ester derivatives (C2) with hydrazine hydrat in ethanol. Compound (C3) from the reaction with different aromatic aldehydes in absolute ethanol gave the Schiff′s bases (C4,C5). The product compounds were characterized by FT-IR, U.V and 1HNMR spectra and the biological activities were studied as antibacterial.

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