The inclusion mode, characterization and cytotoxic activity evaluation of host-guest complex by β-cyclodextrin trimer with podophyllotoxin

Podophyllotoxin (PPT) has a powerful anti-tumor effect on many types of tumors. Its non-specific toxicity and limited solubility in water make it difficult to use in clinical settings unfortunately. Macrocyclic molecules such as cyclodextrins provide a method to improve the water solubility of guest molecules by studying the host-guest interaction. In this study, the molecular recognition behavior of PPT as a guest was studied with β-cyclodextrin trimer (β-CD3) as the host. The results of DOSY NMR and ROESY NMR indicated that the three cavities of β-CD3 form an intramolecular inclusion complex with its own three triazoles. After adding PPT to intramolecular inclusion system, PPT molecule would compete with triazoles of β-CD3 for the cavity site, leading to the destroy of intramolecular inclusion complex and forming a 1:1 inclusion complex with a stability constant of 11710 M−1. In addition, PPT inclusion complex still maintained PPT's effective anti-cancer activity and the water solubility of PPT inclusion complex was 300 times higher than that of free PPT. Moreover, normal human colonic epithelial cells CCD841was essentially unaffected by β-CD3. Our research presents a concept for the advancement and utilization of β-CD3.