1887

Abstract

Tuberculosis (TB) is the leading cause of global morbidity and mortality caused by an infectious disease, with over 10 million new cases emerging in 2017. This global emergency is exacerbated by the emergence of multi-drug and extensively-drug resistant TB, therefore new drugs and new drug targets are urgently required. From a whole-cell phenotypic screen we identified a series of nitrogen-containing heterocyclic compounds that elicit potent anti-mycobacterial activity with MIC values <10 µM against Mycobacterium tuberculosis. Interestingly, this series of compounds demonstrate no detectable drug resistance in mycobacteria. Mode of action and target deconvolution studies suggest that these compounds inhibit mycobacterial growth by interfering with late-stage mycolic acid biosynthesis. In addition, these compounds exhibit a suitable toxicological and PK/PD profile that paves the way for further development as an anti-TB chemotherapy.

Loading

Article metrics loading...

/content/journal/acmi/10.1099/acmi.ac2019.po0419
2019-04-08
2019-12-15
Loading full text...

Full text loading...

http://instance.metastore.ingenta.com/content/journal/acmi/10.1099/acmi.ac2019.po0419
Loading

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error