取代基团对含噻二唑片段截短侧耳素衍生物抑制鸡毒支原体活性的影响

Influence of substituent groups on the antibacterial effect of pleuromutilin derivatives with thiadiazole moiety against Mycoplasma gallisepticum

【目的】为研发抗鸡毒支原体感染的药物提供试验依据。【方法】合成18种C14支链含噻二唑片段的截短侧耳素衍生物,采用高分辨质谱进行结构确证,通过体外药敏试验研究所合成苯环取代基衍生物对鸡毒支原体抑菌活性的影响。【结果】化合物12、15和17对鸡毒支原体S6的最小抑菌质量浓度(Minimum inhibitory concentration,MIC)均为0.125 0μg·mL^(-1),化合物18和对照泰妙菌素对鸡毒支原体S6的MIC值最高,均为0.015 6μg·m L^(-1),化合物18氨基被苯甲酰基化后所得化合物17的抗菌活性减弱。【结论】化合物18可作为候选化合物进行深入研究,以开发新的抗支原体感染药物。

【Objective】 To provide experimental data for the research and development of new antibacterials against Mycoplasma gallisepticum.【Method】Eighteen analogues of pleuromutilin possessing thiadiazole moieties at the C14 chains were synthesized. High resolution mass spectrometry was used to verify the structures of the synthesized compounds. Influence of substituted benzene on the antibacterial effects of these pleuromutilin derivatives against M. gallisepticum were investigated by in vitro drug sensitivity tests.【Result】The obtained MIC values revealed that analogues 12, 15 and 17 exhibited potential antibacterial activities against M. gallisepticum S6 strain with MIC of 0.125 0 μg·mL^-1. Analogue 18 and Tiamulin （control） showed the most potent antibacterial activities against S6 strain in vitro with MIC of 0.015 6μg·mL^-1. Analogue 17, which was the product from benzoylation of the amino group of analogue 18, had lower antibacterial activity compared with analogue 18.【Conclusion】 Analogue 18 can be used as a candidate compound for further development of antibacterials against M. gallisepticum.