School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, China.
State Key Laboratory of Natural Medicines and Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.
Molecules. 2018 Dec 14;23(12):3320. doi: 10.3390/molecules23123320.
Antibiotic resistance has become a serious global problem that threatens public health. In our previous work, we found that ocotillol-type triterpenoid saponin showed good antibacterial activity. Based on preliminary structure-activity relationship, novel serious C-3 substituted ocotillol-type derivatives ⁻ were designed and synthesized. The in vitro antibacterial activity was tested on five bacterial strains ( 168, RN4220, DH5α, ATCC19606 and MRSA USA300) and compared with the tests on contrast. Among these derivatives, C-3 position free hydroxyl substituted compounds ⁻, showed good antibacterial activity against Gram-positive bacteria. Furthermore, compound exhibited excellent antibacterial activity with minimum inhibitory concentrations (MIC) values of 2 μg/mL against MRSA USA300 and 4 μg/mL against . The structure-activity relationships of all current ocotillol-type derivatives our team synthesised were summarized. In addition, the prediction of absorption, distribution, metabolism, and excretion (ADME) properties and the study of pharmacophores were also conducted. These results can provide a guide to further design and synthesis works.
抗生素耐药性已成为严重的全球问题，威胁着公众健康。在我们之前的工作中，我们发现毛叶巴豆醇型三萜皂苷具有良好的抗菌活性。基于初步的构效关系，我们设计并合成了新型 C-3 位取代的毛叶巴豆醇型衍生物 ⁻ 。在体外对五种细菌菌株（ 168、RN4220、DH5α、ATCC19606 和 MRSA USA300）进行了抗菌活性测试，并与对照测试进行了比较。在这些衍生物中，C-3 位无游离羟基取代的化合物 ⁻ 对革兰氏阳性菌表现出良好的抗菌活性。此外，化合物 对 MRSA USA300 的最小抑菌浓度（MIC）值为 2μg/mL，对 的 MIC 值为 4μg/mL，表现出优异的抗菌活性。总结了我们团队合成的所有现有毛叶巴豆醇型衍生物的构效关系。此外，还进行了吸收、分布、代谢和排泄（ADME）性质预测和药效团研究。这些结果可为进一步的设计和合成工作提供指导。
