Cucurbit[7]uril as a possible nanocarrier for the antichagasic benznidazole: a computational approach

Benznidazole (BNZ) is one of the most recommended drugs for the acute phase of Chagas disease. However, its use has some limitations like low aqueous solubility, low biodisponibility, and considerable toxicity. To overcome these shortcomings, the use of nanocarrier agents is an interesting strategy that has been largely used in drug delivery. Therefore, herein molecular dynamics (MD) simulations and potential of mean force (PMF) technique were used to study the encapsulation of the BNZ into beta-cyclodextrin (beta-CD) and curcubit[7]uril (CB[7]) cavities in aqueous solution. Along the 50 ns of MD trajectory, the BNZ kept complexed with CB[7] and beta-CD without significantly altering their structures and their second solvation shell. In the encapsulation process, the BNZ excluded 6 and 7 water molecules from the interior of CB[7] and beta-CD, respectively. Both hosts were able to encapsulate the hydrophobic and hydrophilic groups of the BNZ guest. However, the PMF calculations showed that the BNZ@CB[7] complex is almost three times more stable than the BNZ@beta-CD complex, with binding energies respectively equal to - 60.8 and - 21.8 kJ mol(-1). Therefore, we highlight the CB[7] as a new macrocyclic host for drug delivery of BNZ that may be more efficient than the beta-CD. [GRAPHICS.]