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 β-cyclodextrin (β-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 β-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 β-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@β-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 β-CD.

中文翻译：

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Cucurbit[7]uril 作为抗恰加斯药苯并硝唑的可能纳米载体：一种计算方法

苄硝唑（BNZ）是最推荐用于治疗恰加斯病急性期的药物之一。然而，它的使用有一些局限性，如低水溶性、低生物分解性和相当大的毒性。为了克服这些缺点，纳米载体剂的使用是一种有趣的策略，已广泛用于药物递送。因此，本文使用分子动力学 (MD) 模拟和平均力潜力 (PMF) 技术来研究 BNZ 在 β-环糊精 (β-CD) 和葫芦素 [7] 脲 (CB[7]) 腔中的包封水溶液。沿着 50 ns 的 MD 轨迹，BNZ 与 CB[7] 和 β-CD 保持复合，而没有显着改变它们的结构和它们的第二溶剂化壳。在封装过程中，BNZ分别从CB[7]和β-CD的内部排除了6个和7个水分子。两种主体都能够封装 BNZ 客体的疏水基团和亲水基团。然而，PMF 计算表明 BNZ@CB[7] 复合物的稳定性几乎是 BNZ@β-CD 复合物的三倍，结合能分别等于 - 60.8 和 - 21.8 kJ mol-1。因此，我们强调 CB[7] 作为一种新的大环宿主，用于 BNZ 的药物递送，可能比 β-CD 更有效。