Salmon sperm DNA binding study to cabozantinib, a tyrosine kinase inhibitor: Multi-spectroscopic and molecular docking approaches.
Int J Biol Macromol
; 182: 1852-1862, 2021 Jul 01.
Article
em En
| MEDLINE
| ID: mdl-34062156
ABSTRACT
In the current work, the binding interaction of cabozantinib with salmon sperm DNA (SS-DNA) was studied under simulated physiological conditions (pH 7.4) using fluorescence emission spectroscopy, UV-Vis absorption spectroscopy, viscosity measurement, ionic strength measurement, FT-IR spectroscopy, and molecular modeling methods. The obtained experimental data demonstrated an apparent binding interaction of cabozantinib with SS-DNA. The binding constant (Kb) of cabozantinib with SS-DNA evaluated from the Benesi-Hildebrand plot was equal to 5.79 × 105 at 298 K. The entropy and enthalpy changes (∆S0 and ∆H0) in the binding interaction of SS-DNA with cabozantinib were 44.13 J mol-1 K-1 and -19.72 KJ mol-1, respectively, demonstrating that the basic binding interaction forces are hydrophobic and hydrogen bonding interactions. Results from UV-Vis absorption spectroscopy, competitive binding interaction with rhodamine B or ethidium bromide, and viscosity measurements revealed that cabozantinib binds to SS-DNA via minor groove binding. The molecular docking results revealed that cabozantinib fits into the AT-rich region of the B-DNA minor groove and the binding site of cabozantinib was 4 base pairs long. Moreover, cabozantinib has eight active torsions, implying a high degree of flexibility in its structure, which played a significant role in the formation of a stable cabozantinib-DNA complex.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Piridinas
/
Salmão
/
Análise Espectral
/
Espermatozoides
/
DNA
/
Inibidores de Proteínas Quinases
/
Simulação de Acoplamento Molecular
/
Anilidas
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article