The Binding Mechanism Between Cyclodextrins and Anticancer Drug Noscapine: A Spectroscopic and Molecular Docking Study.

Abstract

In this paper the binding of noscapine (NOS) as an anticancer drug with poor bioavailability and low solubility with beta and methyl-beta cyclodextrins (β-CD and M-β-CD) as the biocompatible drug carriers were discussed using ultraviolet-visible, fluorescence and nuclear magnetic resonance spectroscopy, as well as molecular docking. The absorption of NOS changed when it was bound to both cyclodextrins, resulting in a hyperchromic shift. It formed a 1:1 stoichiometry inclusion complex with both cyclodextrins according to the Benesi-Hildebrand equation. The binding affinity was larger in NOS-M-β-CD (5.9 (± 0.66) × 103 M- 1) than NOS-β-CD (3.7 (± 0.22) × 103 M- 1) complex. The fluorescence emission band of NOS at 408nm was quenched when NOS was complexed with β-CD, and enhanced in the presence of M-β-CD, while the shoulder at 350nm was enhanced selectively when NOS was complexed with M-β-CD. The fluorescence quenching of NOS with β-CD showed a negative deviation from the Stern-Volmer. The thermodynamic parameters have been estimated with the help of the Van't Hoff equation in different temperatures, and a dynamic mechanism was proposed for quenching. Also, both ΔH and ΔS have positive values thus the main interactions result in hydrophobic forces. Moreover, the negative value of ΔG indicates that the bonding process is spontaneous. 1H NMR chemical shift changes were observable for NOS and both CDs protons due to the chemical environment changes of some nuclei upon complexation. The molecular docking results revealed that the 1:1 inclusion complex possesses a good molecular shape complementarity score for their most probable structures, and indicated that the M-β-CD inclusion system gave the higher complexation efficiency. The binding energy values for β-CD and M-β-CD were determined to be -6.7 and - 9.5kcal/mol, respectively. These findings suggest the same as the result of experimental tests that the NOS-M-β-CD complex is more stable than the NOS-β-CD complex.