Bacterial resistance to most of the available antibiotics has stimulated the discovery of novel efficacious antibacterial agents. Bedaquiline is first of its type that has been specifically introduced for the management of MDR‐TB in combination with other drugs. In this study, a series of isoniazid/ethambutol/pyrazinamide/‐quinoline conjugates based on the structures of bedaquiline were designed and synthesized. Biological activity tests revealed that some of isoniazid/ethambutol/quinoline conjugates have useful antibiotic activity against MTB H37Rv (MIC: 2.0–8.0 μg/ml). Furthermore, molecular docking calculations were performed for the most potent inhibitor to show its binding interactions within the active site of the possible target protein. Overall, these compounds represent novel valuable starting point with potent antimycobacterial activity and deserve further structural modifications.

中文翻译：

---

一种开发新型抗分枝杆菌活性候选药物的基于结构的策略：合成，生物学评估和对接研究

对大多数可用抗生素的细菌耐药性刺激了新型有效抗菌剂的发现。贝达喹啉是首个专门用于与其他药物联合治疗耐多药结核病的药物。在这项研究中，基于苯达喹啉的结构，设计并合成了一系列异烟肼/乙胺丁醇/吡嗪酰胺/喹啉共轭物。生物活性测试表明，一些异烟肼/乙胺丁醇/喹啉结合物对MTB H37Rv（MIC：2.0–8.0μg/ ml）具有有用的抗生素活性。此外，对最有效的抑制剂进行了分子对接计算，以显示其在可能的靶蛋白活性位点内的结合相互作用。全面的，