摘要
The emergence of drug-resistant tuberculosis has created an urgent need for new anti-tubercular agents. Here, we report thediscovery of a series of macrolides called sequanamycins with outstanding in vitro and in vivo activity against Mycobacteriumtuberculosis (Mtb). Sequanamycins are bacterial ribosome inhibitors that interact with the ribosome in a similar manner to classicmacrolides like erythromycin and clarithromycin, but with binding characteristics that allow them to overcome the inherentmacrolide resistance of Mtb. Structures of the ribosome with bound inhibitors were used to optimize sequanamycin to produce theadvanced lead compound SEQ-9. SEQ-9 was efficacious in mouse models of acute and chronic TB as a single agent, and itdemonstrated bactericidal activity in a murine TB infection model in combination with other TB drugs. These results supportfurther investigation of this series as TB clinical candidates, with the potential for use in new regimens against drug-susceptibleand drug-resistant TB.
出处
《四川生理科学杂志》
2023年第2期230-230,共1页
Sichuan Journal of Physiological Sciences
