Cucurbit[n]urils (CB[n], n = 5,
6, 7, 8, 10, 14) and their derivatives due to the
hydrophobic cavities and polar carbonyl portals have been considerably
explored for their potential uses as drug delivery systems. It is
important to understand how these macrocyclic compounds interact with
guests. Camptothecin (CPT), as a natural alkaloid, is a topoisomerase
inhibitor with antitumor activity against breast, pancreas, and lung
cancers. The application of this drug in cancer therapy is restricted
due to its low aqueous solubility and high toxicity. Recently, the
complex formation between the cucurbit[7]uril (CB[7])/acyclic cucurbit[4]uril
(aCB[4]) nanocontainers and CPT have been evaluated to overcome the
potential drawbacks of the related drug. Herein, using computational
methods, we identified the interaction mechanism of CPT with CB[7]/aCB[4]s,
which consist of benzene and naphthalene sidewalls (aCB[4]benzene and aCB[4]naphthalene, respectively) since the experimental
approaches have not completely provided information at the molecular
level. Our molecular docking and molecular dynamics (MD) simulations
show that CB[7] and its two acyclic derivatives form stable inclusion
complexes with CPT especially through hydrophobic interactions. We
also found that aCB[4]s with the aromatic sidewalls can attach to
CPT through π–π interactions. This investigation
highlights aCB[4]s due to the structural properties and flexible nature
as better nanocontainers for controlled release delivery of pharmaceutical
agents in comparison with the CB[7] nanocontainer.
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