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通过将含氮杂环与WL001的2-氨基噻唑侧链相连,设计合成了一系列新的截短侧耳素衍生物。用革兰阳性和革兰阴性菌对该系列化合物进行体外抗菌活性测定,合成的大多数化合物不仅在药物敏感菌株中表现出抗菌活性,而且在耐药菌株中也有相同效果。特别值得注意的是具有饱和氮杂环的化合物表现出显著的抗菌活性(0.062 5~8μg·m L-1),优于或类似于阿莫西林、泰妙菌素和左氧氟沙星。此外,15a和15b含有哌啶或吗啉的化合物同样能够有效的抑制革兰阴性菌。本研究为相关截短侧耳素衍生物的设计提供了一个新视野,为进一步研究治疗耐药性致病菌奠定了基础。
A series of new pleuromutilin derivatives were designed and synthesized by linking the nitrogen-containing heterocycle with the side chain of 2-aminothiazole of WL001. In vitro antibacterial activity test of this series of compounds with Gram-positive and Gram-negative bacteria showed that most of the compounds synthesized showed antibacterial activity not only in drug-sensitive strains but also in drug-resistant strains. Of particular note is that compounds with saturated nitrogen heterocycles exhibit significant antibacterial activity (0.062 5 ~ 8 μg · m L -1), superior to or similar to amoxicillin, tiamulin and levofloxacin. In addition, 15a and 15b compounds containing piperidine or morpholine are equally effective at inhibiting Gram-negative bacteria. This study provides a new perspective for the design of pleuromutilin derivatives, which lays the foundation for further research on the treatment of drug-resistant pathogens.