C 或 C 修饰和 D 环重排卡亭-6-酮类似物的合成及抗菌活性。
Synthesis and antibacterial activity of C or C modified and D ring rejiggered canthin-6-one analogues.
机构信息
Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, 22 Xinong Road, Yangling 712100, Shaanxi, China(1).
Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, 22 Xinong Road, Yangling 712100, Shaanxi, China(1); State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Zhangjiang Hi-Tech Park, 201203 Shanghai, China(1).
出版信息
Food Chem. 2018 Jul 1;253:211-220. doi: 10.1016/j.foodchem.2018.01.166.
Thirty-one canthin-6-one analogues, mainly including C or C or D ring modified canthin-6-ones, were designed and synthesized in order to study their antibacterial activity and structure-activity relationships. The analogue 28 with the highest bioactivity had a peak minimum inhibitory concentration of 4 μg/ml and showed low cytotoxicity against L02 cells and good "drug-like" properties. The antibacterial effect of 28 was characterized further by scanning electron microscopy, cytoplasmic β-galactosidase leakage assay, molecular docking evaluation, UV-visible analysis and isothermal titration calorimetry (ITC) measurement. The results showed that 28 may exert its bactericidal effect by damaging bacterial cell membranes and disrupting the function of DNA topoisomerases, both of which could lead to rapid cell death.
为了研究其抗菌活性和构效关系，设计并合成了 31 种康定酮类似物，主要包括 C 或 C 或 D 环修饰的康定酮类似物。具有最高生物活性的类似物 28 的最小抑菌浓度峰值为 4μg/ml，对 L02 细胞的细胞毒性低，且具有良好的“类药性”。通过扫描电子显微镜、细胞质β-半乳糖苷酶渗漏测定、分子对接评价、紫外-可见分析和等温热力学滴定（ITC）测量进一步表征了 28 的抗菌作用。结果表明，28 可能通过破坏细菌细胞膜和干扰 DNA 拓扑异构酶的功能发挥杀菌作用，这两者都可能导致细胞迅速死亡。
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