| 王博阳,史坤雄,赵广健,等.肝X-受体激动剂马尾藻甾醇的体外抗结核活性研究[J].中国海洋药物,2020,39(5):23-28. |
| 肝X-受体激动剂马尾藻甾醇的体外抗结核活性研究 |
| Anti-tuberculosis activities in vitro of LXR agonist saringosterol |
| 投稿时间：2020-03-21 修订日期：2020-04-29 |
| DOI： |
| 中文关键词: 马尾藻甾醇 差向异构体 结核分枝杆菌 芳胺N-乙酰基转移酶 抗结核 |
| English Keywords:Saringosterol 24S-saringosterol Mycobacterium tuberculosis, Arylamine N-Acetyltransferase anti-tuberculosis |
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| 中文摘要: |
| 目的 评价马尾藻甾醇及其24-差向异构体的抗结核活性。方法 运用半制备HPLC法分到马尾藻甾醇异构体,1H-NMR鉴定异构体的化学结构；采用倍比稀释法测定化合物对结核分枝杆菌Mycobacterium tuberculosis的最小抑菌浓度(minimal inhibit concentration, MIC)、单独使用及联合用药的杀菌作用；采用PNPA法评价化合物对芳胺N-乙酰基转移酶(arylamine N-acetyltransferases, NAT)的抑制作用,并使用ledock go软件进行分子虚拟对接实验。结果 获得24S-和24R-马尾藻甾醇；马尾藻甾醇、24S异构体和24R异构体对M. tuberculosis的MIC值分别是25 μM、12.5 μM和 >100μM,对NAT蛋白的抑制率分别为45.27%、46.95%和29.20%。马尾藻甾醇和24S异构体还能增强氧氟沙星的杀菌作用。从数值上看,24S异构体活性强于24R异构体,分子对接实验提示24S异构体与NAT蛋白之间的结合比24R异构体更牢固。结论 马尾藻甾醇及其24S异构体在体外对结核分枝杆菌具有杀菌作用,可能与细菌胆固醇代谢有关,尚待深入研究。 |
| English Summary: |
| Objective To investigate the anti-tuberculous activities of saringosterol and its 24- epimers. Method Semi-PHPLC was used to separate saringosterol epimers and 1H-NMR was employed to identify chemical structures. The doubling dilution method was used to determine the minimum inhibitory concentration (MIC) of the compounds on Mycobacterium tuberculosis, and bactericidal effect of single and combined treatment. PNPA method was used to evaluate the inhibitory effect of compounds on arylamine N-acetyltransferases (NAT), and ledock go software was used for molecular docking experiments. Result 24 epimers of saringosterol were purified and identified. The MIC values of saringosterol, 24S epimer, and 24R epimerr against Mycobacterium tuberculosis were 25 μM, 12.5 μM, and > 100μM, respectively, and their inhibition effects on NAT were 45.27%、46.95% and 29.20%, respectively. 24S epimer was more active than the 24R epimer. Saringosterol and its 24S epimer enhanced the bactericidal effect of ofloxacin. Molecular docking showed that the binding between 24S epimer and NAT protein was stronger than that of 24R epimer. Conclusion Saringosterol and 24S-saringosterol have a bacteriocidal effect in vitro. The mechanism may be related to bacterial cholesterol metabolism, which needs further studies. |
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