Indoleamides are active against drug-resistant Mycobacterium tuberculosis

Shichun Lun, Haidan Guo, Oluseye K. Onajole, Marco Pieroni, Hendra Gunosewoyo, Gang Chen, Suresh K. Tipparaju, Nicole C. Ammerman, Alan P. Kozikowski and William R. Bishai ()
Additional contact information
Shichun Lun: Center for Tuberculosis Research, Johns Hopkins University School of Medicine
Haidan Guo: Center for Tuberculosis Research, Johns Hopkins University School of Medicine
Oluseye K. Onajole: College of Pharmacy, University of Illinois at Chicago
Marco Pieroni: College of Pharmacy, University of Illinois at Chicago
Hendra Gunosewoyo: College of Pharmacy, University of Illinois at Chicago
Gang Chen: College of Pharmacy, University of Illinois at Chicago
Suresh K. Tipparaju: College of Pharmacy, University of Illinois at Chicago
Nicole C. Ammerman: Center for Tuberculosis Research, Johns Hopkins University School of Medicine
Alan P. Kozikowski: College of Pharmacy, University of Illinois at Chicago
William R. Bishai: Center for Tuberculosis Research, Johns Hopkins University School of Medicine

Nature Communications, 2013, vol. 4, issue 1, 1-8

Abstract: Abstract Responsible for nearly two million deaths each year, the infectious disease tuberculosis remains a serious global health challenge. The emergence of multidrug- and extensively drug-resistant strains of Mycobacterium tuberculosis confounds control efforts, and new drugs with novel molecular targets are desperately needed. Here we describe lead compounds, the indoleamides, with potent activity against both drug-susceptible and drug-resistant strains of M. tuberculosis by targeting the mycolic acid transporter MmpL3. We identify a single mutation in mmpL3, which confers high resistance to the indoleamide class while remaining susceptible to currently used first- and second-line tuberculosis drugs, indicating a lack of cross-resistance. Importantly, an indoleamide derivative exhibits dose-dependent antimycobacterial activity when orally administered to M. tuberculosis-infected mice. The bioavailability of the indoleamides, combined with their ability to kill tubercle bacilli, indicates great potential for translational developments of this structure class for the treatment of drug-resistant tuberculosis.

Date: 2013
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/ncomms3907 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3907

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms3907

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().