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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Indoleamides are active against drug-resistant mycobacterium tuberculosis
Nature Communications, Volume 4, Article 2907, Year 2013
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Description
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. © 2013 Macmillan Publishers Limited.
Authors & Co-Authors
Lun, Shichun
United States, Baltimore
Johns Hopkins University
Guo, Haidan
United States, Baltimore
Johns Hopkins University
Onajole, Oluseye K.
United States, Chicago
University of Illinois at Chicago
Pieroni, Marco
United States, Chicago
University of Illinois at Chicago
Italy, Parma
Università Di Parma
Gunosewoyo, Hendra
United States, Chicago
University of Illinois at Chicago
Chen, Gang
United States, Chicago
University of Illinois at Chicago
Tipparaju, Suresh K.
United States, Chicago
University of Illinois at Chicago
United States, Cambridge
Merrimack Pharmaceuticals, Inc
Ammerman, Nicole C.
United States, Baltimore
Johns Hopkins University
South Africa, Durban
Africa Health Research Institute
Kozikowski, Alan P.
United States, Chicago
University of Illinois at Chicago
Bishai, William R.
United States, Baltimore
Johns Hopkins University
South Africa, Durban
Africa Health Research Institute
United States, Chevy Chase
Howard Hughes Medical Institute
Statistics
Citations: 133
Authors: 10
Affiliations: 6
Identifiers
Doi:
10.1038/ncomms3907
e-ISSN:
20411723
Research Areas
Cancer