Molecular dynamics study of host–guest interactions between anticancer drugs and Cucurbit[8]uril nanocontainer

Cucurbit[n]urils (CB[n]s) are synthetic molecular containers with unique structural features, containing hydrophobic cavities and polar carbonyl portals. They have widespread applications in various scientific fields, such as drug delivery systems. Paclitaxel (PTX) and Camptothecin (CPT) are natural compounds extensively used as chemotherapy drugs due to their antitumor activity. However, their application is limited by severe side effects and poor aqueous solubility. Consequently, numerous studies have been conducted to overcome these limitations. Several studies have shown that the CB[n] family, especially CB[7], and their derivatives can form stable inclusion complexes with hydrophobic drugs, thereby increasing their solubility in aqueous environments. In this research, molecular docking procedure and molecular dynamics (MD) simulations were utilized to consider the interaction details of PTX and CPT with CB[8]. The results indicate that CB[8] is capable of forming inclusion complexes with both PTX and CPT not only in a 1:1 ratio but also, due to the appropriate cavity size, in a 1:2 stoichiometry, primarily driven by the release of high-energy water molecules from within the CB[8] cavity into the bulk phase. Furthermore, the results suggest the possibility of π-π interactions between the two trapped drugs within the CB[8] cavity during the MD simulation.