Enhancing bio-availability of β-naphthoflavone by supramolecular complexation with 6,6′-thiobis(methylene)-β-cyclodextrin dimer

• 6, 6′-Thiobis(methylene)-β-cyclodextrin dimer (β-CD-S-dimer) was synthesized.
• The β-CD-S-dimer was used to enhance β-naphthoflavone’s water solubility.
• The solubilized β-NF by complexation significantly induced the cytochrome P4501A1 activity.
• β-NF supramolecular complex with β-CD-S-dimer enhanced the bio-functionality of β-NF.
• Various instrumental analyses were performed to verify the formation of a supramolecular complex.

The aryl hydrocarbon receptor (AhR) is a ligand activated transcriptional regulator, which governs key biological processes including detoxification of carcinogens. β-Naphthoflavone (β-NF) is a non-toxic flavonoid, and a potent AhR agonist. Thus, β-NF can induce the representative detoxifying enzyme cytochrome P4501A1, thereby enhancing the detoxification potential. However, its low water solubility hampers the use. We found that supramolecular complexation of β-NF with the synthetic 6,6′-thiobis(methylene)-β-cyclodextrin (β-CD-S) dimer significantly enhanced β-NF’s role as an AhR agonist. The water solubility of β-NF was increased to 469 fold by effective supramolecular complexation with the β-CD-S dimer, and caused significant induction of cytochrome P4501A1. Stable formation of the supramolecular complex of β-NF with β-CD-S-dimer was verified by various analyses. In summary, supramolecular complexation of β-NF with β-CD-S dimer greatly enhanced bio-availability of β-NF as an AhR agonist. Our findings provide an easy, non-destructive, and alternative approach to enhance the bio-availability of therapeutics.