Theoretical and Experimental Studies on Inclusion Complexes of Pinostrobin and β-Cyclodextrins.
Pinostrobin (PNS) belongs to the flavanone subclass of flavonoids which shows several biological activities such as anti-inflammatory, anti-cancerogenic, anti-viral and anti-oxidative effects. Similar to other flavonoids, PNS has a quite low water solubility. The purpose of this work is to improve the solubility and the biological activities of PNS by forming inclusion complexes with β-cyclodextrin (βCD) and its derivatives, heptakis-(2,6-di-O-methyl)-β-cyclodextrin (2,6-DMβCD) and (2-hydroxypropyl)-β-cyclodextrin (HPβCD). The AL-type diagram of the phase solubility studies of PNS exhibited the formed inclusion complexes with the 1:1 molar ratio. Inclusion complexes were prepared by the freeze-drying method and were characterized by differential scanning calorimetry (DSC). Two-dimensional nuclear magnetic resonance (2D-NMR) and steered molecular dynamics (SMD) simulation revealed two different binding modes of PNS, i.e., its phenyl- (P-PNS) and chromone- (C-PNS) rings preferably inserted into the cavity of βCD derivatives whilst only one orientation of PNS, where the C-PNS ring is inside the cavity, was detected in the case of the parental βCD. All PNS/βCDs complexes had a higher dissolution rate than free PNS. Both PNS and its complexes significantly exerted a lowering effect on the IL-6 secretion in LPS-stimulated macrophages and showed a moderate cytotoxic effect against MCF-7 and HeLa cancer cell lines in vitro.
['Kicuntod|Jintawee|J|', 'Sangpheak|Kanyani|K|', 'Mueller|Monika|M|', 'Wolschann|Peter|P|', 'Viernstein|Helmut|H|', 'Yanaka|Saeko|S|', 'Kato|Koichi|K|', 'Chavasiri|Warinthorn|W|', 'Pongsawasdi|Piamsook|P|', 'Kungwan|Nawee|N|', 'Rungrotmongkol|Thanyada|T|']
inclusion complexation pinostrobin β-cyclodextrin biological activity steered molecular dynamics simulation