Key Laboratory of Marine Drugs, The Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.
State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, College of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin 541004, China.
Mar Drugs. 2024 Mar 16;22(3):135. doi: 10.3390/md22030135.
With the emergence of drug-resistant strains, the treatment of tuberculosis (TB) is becoming more difficult and there is an urgent need to find new anti-TB drugs. , as a model organism of , can be used for the rapid and efficient screening of bioactive compounds. The 14-membered resorcylic acid lactones (RALs) have a wide range of bioactivities such as antibacterial, antifouling and antimalarial activity. In order to further study their bioactivities, we initially constructed a 14-membered RALs library, which contains 16 new derivatives. The anti- activity was evaluated in vitro. Derivatives , , and exhibited promising activity with MIC values of 80, 90, 80 and 80 μM, respectively. The preliminary structure-activity relationships showed that the presence of a chlorine atom at C-5 was a key factor to improve activity. Further studies showed that markedly inhibited the survival of and significantly reduced the dosage of positive drugs isoniazid and rifampicin when combined with them. These results suggest that is a bioactive compound capable of enhancing the potency of existing positive drugs, and its effective properties make it a very useful leads for future drug development in combating TB resistance.
随着耐药菌株的出现，结核病（TB）的治疗变得更加困难，迫切需要寻找新的抗结核药物。 作为 的模式生物，可以用于快速高效地筛选生物活性化合物。 具有广泛的生物活性，如抗菌、防污和抗疟活性。 为了进一步研究它们的生物活性，我们最初构建了一个 14 元环的 resorcylic 酸内酯（RALs）文库，其中包含 16 个新衍生物。 在体外评估了它们的抗 活性。 衍生物 、 、 和 表现出有希望的活性，MIC 值分别为 80、90、80 和 80 μM。 初步的结构-活性关系表明，C-5 位上存在氯原子是提高活性的关键因素。 进一步的研究表明 显著抑制了 和 的存活，并显著降低了与阳性药物异烟肼和利福平联合使用时的剂量。 这些结果表明 是一种能够增强现有阳性药物效力的生物活性化合物，其有效特性使其成为未来抗结核耐药性药物开发非常有用的先导化合物。
