熊果酸衍生物的合成及其抗菌活性评价

目的 对熊果酸A环进行结构修饰,并研究其体外抗菌活性.方法 以熊果酸(1)为原料,合成A环不同的熊果酸衍生物2-13,并用大肠杆菌、铜绿假单胞菌、金黄色葡萄球菌、表皮葡萄球菌、藤黄微球菌和枯草杆菌这6种细菌对熊果酸衍生物进行体外抗菌活性筛选.结果 大部分熊果酸衍生物显示很强的抗菌活性,其中化合物7对金黄色葡萄球菌的MIC值为6.3μmol/L,化合物8和化合物9对藤黄微球菌的MIC值分别为12.5μmol/L和6.3μmol/L,化合物11对六个菌种的MIC值均为3.1μmol/L,化合物12对大肠杆菌、铜绿假单胞菌、金黄色葡萄球菌、表皮葡萄球菌的MIC值为3.1μmol/L.结论 熊果酸A环化学结构修饰能够有效提高其抗菌活性,尤其是A环引入双键或环氧基,可为熊果酸抗菌衍生物的进一步研发提供依据.

Synthesis and Antibacterial Evaluation of Ursolic Acid Derivatives

Objective To synthesize ursolic acid (UA) derivatives and investigate its antibacterial activities. Methods UA (1) as the starting material, UA derivatives (2-13) were modified by functional groups in ring A and its antibacterial activities were evaluated by Escherichia coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa), Staphylococcus aureus (S. aureus), Staphylococcus epidermidis (S. epidermidis), Micrococcus luteus (M. luteus) and Bacillus subtilis (B. subtilis). Results Most of UA derivatives displayed potent antibacterial activity, such as compound 7 against S. aureus with MIC of 6.3 μM, compound 8 and 9 against M. luteus with MICs of 12.5 μM and 6.3 μM, respectively, compound 11 against six bacteria strains with a same MIC of 3.1 μM, and compound 12 against E. coli, P. aeruginosa, S. aureus and S. epidermidis, with a same MIC of 3.1 μM. Conclusion All of the derivatives showed stronger antibacteral activities than UA in vitro, especially, when an epoxy or unsaturated moiety was introduced in ring A. It may be used for the future research on antibacterial agents from UA derivatives.