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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 Sep 01 2026
Journal Name
Indian Journal Of Heterocyclic Chemistry
Design, synthesis of various cyclic derivatives of pyrimidine and investigation of antibacterial behavior in vitro and in silico
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A new series of cyclic coumarin-fluorocytosine hybrid conjugates (N1-N6) was synthesized through microwave technology. The synthetic plan involved the formation of the required Schiff base N, followed by the transformation of the azomethine functional group of the Schiff base N to oxazepine and imidazolidone rings. The antimicrobial activity of the synthesized compounds N-N6 was assessed against Gram-positive bacteria (Staphylococcus aureus and Staphylococcus epidermidis) and Gram-negative bacteria (Escherichia coli, Pseudomonas, and Klebsiella) using the disk diffusion method. Compounds N4 and N5 showed the highest activity against S. aureus (24 mm inhibition), with N5 also demonstrating superior inhibition against Klebsiella and P

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Publication Date
Wed Jun 26 2019
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Synthesis of Acetylenic Derivatives of a Substituted 1, 3, 4-Thiadiazole as Antibacterial Agents
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Publication Date
Thu May 25 2023
Journal Name
Results In Chemistry
Synthesis and characterization of (E)-4-(((4-(5-mercapto-1, 3, 4-oxadiazol-2-yl) phenyl) amino) methyl)-2-methoxyphenol as a novel corrosion inhibitor for mild-steel in acidic medium
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Metal corrosion is a destructive process for many industrial operations, including oil well acidizing and acid pickling. Therefore, numerous efforts made by many researchers to control the steel corrosion. In the present work, A (E)-4-(((4-(5-mercapto-1,3,4-oxadiazol-2-yl) phenyl) amino) methyl)-2-methoxyphenol (MOPM) has been synthesized and characterized as a new corrosion inhibitor for mild steel in 0.1 M hydrochloric acid. FTIR and 1 HNMR were used in the diagnosis of MOPM, while electrochemical polarization technique was employed to test the performance of inhibitor at various temperatures and inhibitor concentrations. Electrochemical studies showed that MOPM acts as a mixed-type inhibitor with a maximum inhibition efficiency of

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Publication Date
Sun Jan 01 2023
Journal Name
Results In Chemistry
Synthesis and characterization of (E)-4-(((4-(5-mercapto-1, 3, 4-oxadiazol-2-yl) phenyl) amino) methyl)-2-methoxyphenol as a novel corrosion inhibitor for mild-steel in acidic medium
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Publication Date
Sat May 30 2026
Journal Name
Iraqi Journal Of Science
Synthesis and Evaluation of 3-(4-bromobenzyl)-2-mercaptoquinazolin-4(3H)-one as a Corrosion Inhibitor for carbon steel CS45  in 1M HCl
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     In this study, a mercapto-quinazolinone derivative, 3-(4-Bromobenzyl)-2-mercaptoquinazolin-4(3H)-one (compound B), was synthesized and assessed as a corrosion inhibitor for carbon steel (CS45) in 1M hydrochloric acid. The synthesis began with anthranilic acid and involved two main steps: first, the formation of a thiocyanate intermediate, followed by its reaction with anthranilic acid to produce compound B. The chemical structure of the synthesized compound was confirmed using FT-IR, 1H-NMR, and 13C-NMR techniques. The corrosion inhibition performance of compound B was evaluated at different concentrations (0.01, 0.05, 0.1, and 0.3 M) and temperatures (293, 303, and 313 K) in acidic media. Potentiodynamic polarization measu

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Publication Date
Sun Mar 30 2025
Journal Name
Iraqi Journal Of Science
Ru+3, Rh+3, Pd+2,Pt+4 and Au+3 Metal ions Complexes with Azo Derived from 4-Aminomethyl-cyclohexane carboxylic acid Synthesis, Characterization, Thermal Study and Antioxidant Activity
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The researchers aimed to develop a novel azo ligand as a continuation of their prior investigations. They synthesized the ligand, identified as N-(3-acetyl-2- hydroxy-5-methyl-phenyl)N-(4-carboxy-cyclohexylmethyl)-diazonium salt, and proceeded to synthesize a series of chelate complexes with Ru+3, Rh+3, Pd+2, Pt+4, and Au+3 ions. Characterization of these compounds includes advanced techniques including elemental analysis, UV-Vis spectroscopy, FT-IR spectroscopy, LC-Mass spectrometry, NMR spectroscopy plus thermal analysis, conductivity measurements, magnetic quantification using TGA and DSC are used to further clarify the and synthesized complexes have been developed.Analysis revealed that the complexes formed with Ru+3, Rh+3, Pt+4, and Au

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Publication Date
Mon Jan 01 2024
Journal Name
Journal Of Molecular Structure
Synthesis, biomedical activities, and molecular docking study of novel chromone derivatives
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Publication Date
Sat Feb 28 2026
Journal Name
Journal Of Molecular Structure
Synthesis, Characterization, Molecular Docking and anti-corrosion activities of new Pyrimidine Derivatives
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Publication Date
Sun Mar 01 2026
Journal Name
Journal Of Molecular Structure
Synthesis, characterization, molecular docking and anti-corrosion activities of new pyrimidine derivatives
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In the present study, chalcone derivatives were synthesized via the Claisen-Schmidt condensation of 2-methyl acetanilide or 4-nitro acetanilide with p-dimethyl amino benzaldehyde in an ethanolic sodium hydroxide solution. The resulting chalcone reacted with urea or thiourea to produce several novel pyrimidine derivatives. All the synthesized compounds were characterized by FTIR, 1HNMR and 13CNMR spectroscopy. Before the synthesis process, molecular docking studies were performed to evaluate the potential of the synthesized molecules as drug candidates. Thus, molecular docking studies were performed using the CCDC GOLD suite (version 2025). The molecular docking results showed that the synthesized molecules had a noticeable affinity towards

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Publication Date
Thu Jan 01 2015
Journal Name
The International Journal Of Biotechnology,
LACTIC ACID AS SPACER BETWEEN POLY ACRYLIC ACID AND 4- AMINOANTIPYRINE
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