Antibacterial activity evaluation of synthetic novel pleuromutilin derivatives in vitro and in experimental infection mice

作者：Deng, Yu; Wang, Xiao-Zhong; Huang, Shu-Heng; Li, Cheng-Hong^*

来源：European Journal of Medicinal Chemistry, 2019, 162: 194-202.

DOI：10.1016/j.ejmech.2018.11.006

• Antibacterial activity
• In vivo efficacy
• Pleuromutilin derivatives
• Pyrrolopyrimidine
• Gram-positive bacteria

A series of novel pleuromutilin derivatives embracing 7H-pyrrolo[2,3-d]pyrimidine moiety were synthesized and evaluated for their in vitro antibacterial activity against Gram-positive and Gram-negative pathogens as well as in vivo efficacy in lethal systemic infected mice. Most compounds displayed good in vitro potency against MSSA, MRSA, MSSE, MRSE and E. faecium (MIC = 0.0625-4 mu g/mL), especially 15a, 15b and 15o showed excellent activity that even more active than the comparator valnemulin. The in vivo efficacy investigation exhibited compound 15a (ED50 = 16.0 mg/kg) had comparable activity to valnemulin (ED50 = 13.5 mg/kg). The results provided by the dose-response study demonstrated 15a can supply infected mice with 70% survival rate at dose of 40 mg/kg via intragastric (i.g.) administration.

• 出版日期2019-1-15
• 单位重庆市畜牧科学院; 重庆大学