Interactive Analysis of UTX-114 Family With EGFR-tyk: Molecular Features of Acetyl Glycosylated Gefitinib.
Anticancer Res
; 44(8): 3587-3591, 2024 Aug.
Article
em En
| MEDLINE
| ID: mdl-39060048
ABSTRACT
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 ANDMETHODS:
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 IC50 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.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Simulação de Acoplamento Molecular
/
Receptores ErbB
/
Gefitinibe
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article