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 accessAbstract
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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The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics
Lundberg, J. O., Weitzberg, E., & Gladwin, M. T. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2466 · Cited by 2,739
Identification of nitric oxide synthase as a protective locus against tuberculosis
MacMicking, J. D., North, R. J., LaCourse, R., Mudgett, J. S., Shah, S. K., & Nathan, C. F. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.10.5243 · Cited by 1,180
Tuberculosis — metabolism and respiration in the absence of growth
Boshoff, H. I. M., & Barry, C. E. (2005) · Nature Reviews Microbiology · doi:10.1038/nrmicro1065 · Cited by 448
Self-citation
Cited by
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Bhutani, P., Joshi, G., Raja, N., Bachhav, N., Rajanna, P. K., Bhutani, H., Paul, A. T., & Kumar, R. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c01786 · Cited by 815
Benzothiazinones Kill Mycobacterium tuberculosis by Blocking Arabinan Synthesis
Makarov, V., Manina, G., Mikusova, K., Möllmann, U., Ryabova, O., Saint-Joanis, B., Dhar, N., Pasca, M. R., Buroni, S., Lucarelli, A. P., et al. (2009) · Science · doi:10.1126/science.1171583 · Cited by 740
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Dartois, V. A., & Rubin, E. J. (2022) · Nature Reviews Microbiology · doi:10.1038/s41579-022-00731-y · Cited by 490
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Baek, S.-H., Li, A. H., & Sassetti, C. M. (2011) · PLoS Biology · doi:10.1371/journal.pbio.1001065 · Cited by 324
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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- 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).
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