Sansanmycin natural product analogues as potent and selective anti-mycobacterials that inhibit lipid I biosynthesis View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-03-01

AUTHORS

Anh T. Tran, Emma E. Watson, Venugopal Pujari, Trent Conroy, Luke J. Dowman, Andrew M. Giltrap, Angel Pang, Weng Ruh Wong, Roger G. Linington, Sebabrata Mahapatra, Jessica Saunders, Susan A. Charman, Nicholas P. West, Timothy D. H. Bugg, Julie Tod, Christopher G. Dowson, David I. Roper, Dean C. Crick, Warwick J. Britton, Richard J. Payne

ABSTRACT

Tuberculosis (TB) is responsible for enormous global morbidity and mortality, and current treatment regimens rely on the use of drugs that have been in use for more than 40 years. Owing to widespread resistance to these therapies, new drugs are desperately needed to control the TB disease burden. Herein, we describe the rapid synthesis of analogues of the sansanmycin uridylpeptide natural products that represent promising new TB drug leads. The compounds exhibit potent and selective inhibition of Mycobacterium tuberculosis, the etiological agent of TB, both in vitro and intracellularly. The natural product analogues are nanomolar inhibitors of Mtb phospho-MurNAc-pentapeptide translocase, the enzyme responsible for the synthesis of lipid I in mycobacteria. This work lays the foundation for the development of uridylpeptide natural product analogues as new TB drug candidates that operate through the inhibition of peptidoglycan biosynthesis. More... »

PAGES

14414

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ncomms14414

DOI

http://dx.doi.org/10.1038/ncomms14414

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1084128797

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28248311


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