Interactive Analysis of UTX-114 Family With EGFR-tyk: Molecular Features of Acetyl Glycosylated Gefitinib.

Autor: Ohkura K; Graduate School of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Japan; kohkura@suzuka-u.ac.jp., Tabata A; Department of Biological Science and Technology, Life System, Institute of Technology and Science, The University of Tokushima Graduate School, Tokushima, Japan., Uto Y; Department of Biological Science and Technology, Life System, Institute of Technology and Science, The University of Tokushima Graduate School, Tokushima, Japan.
Jazyk: angličtina
Zdroj: Anticancer research [Anticancer Res] 2024 Aug; Vol. 44 (8), pp. 3587-3591.
DOI: 10.21873/anticanres.17181
Abstrakt: Background/aim: Acetyl glucose adducts (UTX-114, -115, and -116) were prepared from gefitinib, and their characteristics (e.g., anticancer activity, structural property) were analyzed.
Materials and Methods: Cytotoxicity and radiosensitizing properties of the UTX-114 family were examined using A431 cells. Supramolecular associations between the UTX-114 family compounds and the tyrosine kinase domain of epidermal growth factor receptor (EGFR-tyk) were also examined. The interactive analyses of the UTX-114 family compounds with EGFR-tyk were performed using docking simulation technique.
Results: The UTX-114 family showed a similar cytotoxicity as gefitinib, yielding IC 50 values of 31.2 μM (gefitinib), 34.3 μM (UTX-114), 36.8 μM (UTX-115), and 39.4 μM (UTX-116). The EGFR-tyk inhibition ratios (IR) of UTX-114, -115, and -116 to gefitinib were 1.515, 0.983, and 0.551, respectively. The EGFR-tyk inhibitory activity of UTX-114 was higher than that of gefitinib. UTX-114 also showed the highest radiosensitizing activity among the tested compounds. UTX-114 expressed 1841 conformers (-8.989~15.718 kcal/mol) with the solvation free energy (dGW) of UTX-114 decreasing with increasing conformational energy, ranging between -354.955~ -260.815 kJ/mol. Interactive energies of gefitinib, UTX-114, -115, and -116 with EGFR-tyk were -123.640, -144.053, -120.830, and -124.658 kcal/mol, respectively.
Conclusion: UTX-114 yielded the lowest interaction energy with EGFR-tyk among tested compounds. Given the association behavior between UTX-114 and EGFR-tyk, along with its other observed properties, UTX-114 appears to be a viable therapeutic possibility.
(Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
Databáze: MEDLINE
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