Antimicrobial activity, safety and pharmacokinetics evaluation of PMTM: A novel pleuromutilin candidate

文献类型： 外文期刊

第一作者： Zhou, Xingqian

作者： Zhou, Xingqian;Zhang, Hongjuan;Zhou, Yuhang;Yuan, Ruili;Pu, Wanxia;Wang, Shengyi;Shang, Ruofeng;Yi, Yunpeng

作者机构：

关键词： PMTM; Antibacterial activity; Safety; Salt form; Pharmacokinetics

期刊名称：BIOMEDICINE & PHARMACOTHERAPY （ 影响因子：7.5； 五年影响因子：7.7 ）

ISSN： 0753-3322

年卷期： 2024 年 179 卷

页码：

收录情况： SCI

摘要： The prevalence of infections by methicillin-resistant Staphylococcus aureus (MRSA) has led to dramatically increased mortality and threated the public health worldwide. Pleuromutilin compound 14-O-[(4-(pyrrolidine-1yl)-6-methylpyrimidine-2-yl) thioacetyl] mutilin (PMTM) is a new antibacterial agent with excellent antibacterial efficacy against Gram positive bacteria. For further developing PMTM as a potential drug against MRSA infections, the in vitro antibacterial efficacy and preclinical safety were explored in this study. The results revealed that PMTM presented the higher anti-MRSA activity, increasing post-antibiotic effect (PAE) and limited potential to develop resistance. In safety evaluation, PMTM demonstrated low cytotoxicity, poor hemolytic activity, tolerable oral acute toxic effects in rats, devoid of mutagenic response and weak inhibitory potential on CYP3A4, but displayed moderate potential hERG K+ channel inhibition. Furthermore, two salts of PMTM with sulfuric acid and hydrochloric acid were prepared and confirmed. The sulfate salt of PMTM exhibited the highest solubility based on powder dissolution experiments and was chosen to evaluate pharmacokinetics properties, in which it displayed improved mouse pharmacokinetics parameters and oral bioavailability. The present study successfully provides a good foundation of PMTM for new antibacterial drug development.

分类号：

  • 相关文献
作者其他论文 更多>>

微信小程序