新型 1,3,4-噁二唑类化合物具有抗结核活性，对耐药结核病的活性有限。
Novel 1,3,4-oxadiazoles as antitubercular agents with limited activity against drug-resistant tuberculosis.
机构信息
Department of Organic Synthesis & Process Chemistry, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500 007, India.
Academy of Scientific & Innovative Research, Ghaziabad, Uttar Pradesh 201002, India.
出版信息
Future Med Chem. 2019 Mar;11(6):499-510. doi: 10.4155/fmc-2018-0378. Epub 2019 Mar 20.
AIM
In recent times, heterocyclic chemotypes are being explored for the development of new antimycobacterials that target the drug-resistant tuberculosis. Here, we are disclosing the 5-substitued 2-mercapto-1,3,4-oxadiazoles as potent antitubercular agents.
METHODOLOGY
A small library of 2-mercapto-1,3,4-oxadiazoles was synthesized using various acids. The compounds were evaluated for antituberculosis activity against M. tuberculosis H37Rv.
RESULTS
Compound 8j was identified as antitubercular lead with MIC of 0.6 μg/ml against M. tuberculosis H37Rv. This compound was nontoxic to CHO-K1 cells and showed selectivity index of 39. Of note, 8j showed antitubercular activity against pre-extensively drug-resistant clinical isolate of Mycobacterium with MIC of 2 μg/ml.
CONCLUSION
This study provides potent antitubercular agent which can be further optimized to discover novel antibiotics.
目的
近年来，人们一直在探索杂环化学型，以开发针对耐药结核病的新型抗分枝杆菌药物。在这里，我们公开了 5-取代的 2-巯基-1,3,4-恶二唑作为有效的抗结核药物。
方法
使用各种酸合成了一个 2-巯基-1,3,4-恶二唑的小文库。评估了化合物对结核分枝杆菌 H37Rv 的抗结核活性。
结果
化合物 8j 被鉴定为具有抗结核作用的先导化合物，对结核分枝杆菌 H37Rv 的 MIC 为 0.6 μg/ml。该化合物对 CHO-K1 细胞无毒性，选择性指数为 39。值得注意的是，8j 对具有 MIC 为 2 μg/ml 的预广泛耐药临床分枝杆菌分离株也具有抗结核活性。
结论
本研究提供了一种有效的抗结核药物，可进一步优化以发现新型抗生素。
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