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Cited by 628

The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.

PA-824 Kills Nonreplicating Mycobacterium tuberculosis by Intracellular NO Release

Open access
Singh, Ramandeep, Manjunatha, Ujjini, Boshoff, Helena I. M., Ha, Young Hwan, Niyomrattanakit, Pornwaratt, Ledwidge, Richard, Dowd, Cynthia S., Lee, Ill Young, Kim, Pilho, Zhang, Liang, Kang, Sunhee, Keller, Thomas H., Jiricek, Jan, Barry, Clifton E.·2008·Science

Abstract

Bicyclic nitroimidazoles, including PA-824, are exciting candidates for the treatment of tuberculosis. These prodrugs require intracellular activation for their biological function. We found that Rv3547 is a deazaflavin-dependent nitroreductase (Ddn) that converts PA-824 into three primary metabolites; the major one is the corresponding des-nitroimidazole (des-nitro). When derivatives of PA-824 were used, the amount of des-nitro metabolite formed was highly correlated with anaerobic killing of Mycobacterium tuberculosis (Mtb). Des-nitro metabolite formation generated reactive nitrogen species, including nitric oxide (NO), which are the major effectors of the anaerobic activity of these compounds. Furthermore, NO scavengers protected the bacilli from the lethal effects of the drug. Thus, these compounds may act as intracellular NO donors and could augment a killing mechanism intrinsic to the innate immune system.

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Crossref · 10.1126/science.1164571

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Metadata

Authors
Singh, R., Manjunatha, U., Boshoff, H. I. M., Ha, Y. H., Niyomrattanakit, P., Ledwidge, R., Dowd, C. S., Lee, I. Y., Kim, P., Zhang, L., Kang, S., Keller, T. H., Jiricek, J., & Barry, C. E.
Venue
Science
Published
2008-11-28
Volume
322
Issue
5906
Pages
1392-1395
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W2145085703
Cited by
628
References
3
FWCI
21.26
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: PA-824 Kills Nonreplicating Mycobacterium tuberculosis by Intracellular NO Release. https://app.cochat.ai/papers/10.1126/science.1164571
The paper
Singh, R., Manjunatha, U., Boshoff, H. I. M., Ha, Y. H., Niyomrattanakit, P., Ledwidge, R., Dowd, C. S., Lee, I. Y., Kim, P., Zhang, L., Kang, S., Keller, T. H., Jiricek, J., & Barry, C. E. (2008). PA-824 Kills Nonreplicating Mycobacterium tuberculosis by Intracellular NO Release. Science. https://doi.org/10.1126/science.1164571

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.