Bedaquiline (BDQ) is a newly approved anti-tuberculosis drug in treating multidrug-resistant tuberculosis. However, it has very poor aqueous solubility and several case reports have proposed that BDQ has potential risk of cardiotoxicity to patients. In this present study, we have explored into employing host-guest interactions between a synthetic receptor, cucurbit[7]uril (CB[7]), and BDQ aiming to improve the solubility and reduce the inherent cardiotoxicity of BDQ. HPLC-UV test on the solubility of BDQ in the absence and in the presence of increasing concentrations of CB[7] suggested a host-dependent guest-solubility enhancements. Cardiovascular studies using an in vivo zebrafish model demonstrated that the cardiotoxicity of BDQ was indeed alleviated upon its complexations by the synthetic receptor. Furthermore, our in vitro antibacterial studies suggested that CB[7] formulated BDQ preserved its antimycobacterial efficacy against Mycobacterium smegmatis. Therefore, CB[7] may become a suitable pharmaceutical excipient in formulating BDQ for improving its physiochemical properties (such as solubility), and for alleviating its side effects (such as cardiotoxicity), while the antimycobacterial efficacy of BDQ may be well maintained.

Bedaquiline（BDQ）是一种新批准的抗结核药物，用于治疗耐多药结核病。但是，它的水溶性很差，一些病例报告表明BDQ对患者具有潜在的心脏毒性风险。在本研究中，我们探索了利用合成受体，葫芦[7]尿素（CB [7]）和BDQ之间的宿主-客体相互作用，旨在提高BDQ的溶解度并降低其固有的心脏毒性。在缺乏和存在浓度不断升高的CB的情况下，对BDQ的溶解度进行HPLC-UV测试[7]，表明了宿主依赖性客体溶解度的提高。使用体内的心血管研究斑马鱼模型证明了BDQ的心脏毒性确实由于其合成受体的复合作用而得到缓解。此外，我们的体外抗菌研究表明，CB [7]配制的BDQ保留了其对耻垢分枝杆菌的抗分枝杆菌功效。因此，CB [7]可能会成为配制BDQ的合适药物赋形剂，以改善BDQ的理化特性（例如溶解度）和减轻其副作用（例如心脏毒性），同时可以很好地保持BDQ的抗分枝杆菌功效。