Tuberculosis (TB) is one of the most fatal diseases and is responsible for the infection of millions of people around the world. Most recently, scientific frontiers have been engaged to develop new drugs that can overcome drug-resistant TB. Following this direction, using a designed scaffold based on the combination of two separate pharmacophoric groups, a series of menadione-derived selenoesters was developed with good yields. All products were evaluated for their in vitro activity against Mycobacterium tuberculosis H37Rv and attractive results were observed, especially for the compounds 8a, 8c and 8f (MICs 2.1, 8.0 and 8.1 μM, respectively). In addition, 8a, 8c and 8f demonstrated potent in vitro activity against multidrug-resistant clinical isolates (CDCT-16 and CDCT-27) with promising MIC values ranging from 0.8 to 3.1 μM. Importantly, compounds 8a and 8c were found to be non-toxic against the Vero cell line. The SI value of 8a (>23.8) was found to be comparable to that of isoniazid (>22.7), which suggests the possibility of carrying out advanced studies on this derivative. Therefore, these menadione-derived selenoesters obtained as hybrid compounds represent promising new anti-tubercular agents to overcome TB multidrug resistance.

结核病（TB）是最致命的疾病之一，是导致全球数百万人感染的原因。最近，科学前沿致力于开发可以克服耐药结核病的新药。按照这个方向，使用基于两个单独的药效基团的组合的设计支架，开发了具有良好收率的一系列甲萘醌衍生的硒酸酯。评估了所有产品的抗结核分枝杆菌H37Rv的体外活性，并观察到了诱人的结果，尤其是对于化合物8a，8c和8f（分别为MIC 2.1、8.0和8.1μM）。另外，8a，8c和8f表现出对多药耐药临床分离株（CDCT-16和CDCT-27）的有效体外活性，其MIC值介于0.8至3.1μM之间。重要的是，发现化合物8a和8c对Vero细胞系无毒。发现8a的SI值（> 23.8）与异烟肼的SI值（> 22.7）相当，这表明对该衍生物进行深入研究的可能性。因此，作为混合化合物获得的这些薄荷脑酮衍生的硒酸酯代表了有望克服结核病多药耐药性的新型抗结核药。