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Sodium borohydride and thiol mediated nitrite release from nitroaromatic antibiotics.
- Source :
-
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2021 Sep 15; Vol. 48, pp. 128245. Date of Electronic Publication: 2021 Jul 07. - Publication Year :
- 2021
-
Abstract
- Nitroaromatic antibiotics are used to treat a variety of bacterial and parasitic infections. These prodrugs require reductive bioactivation for activity, which provides a pathway for the release of nitrogen oxide species such as nitric oxide, nitrite, and/or nitroxyl. Using sodium borohydride and 2-aminoethanol as model reductants, this work examines release of nitrogen oxide species from various nitroaromatic compounds through several characterization methods. Specifically, 4- and 5-nitroimidazoles reproducibly generate higher amounts of nitrite (not nitric oxide or nitroxyl) than 2-nitroimidazoles during the reaction of model hydride donors or thiols. Mass spectrometric analysis shows clean formation of products resulting from nucleophile addition and nitro group loss. 2-Nitrofurans generate nitrite upon addition of sodium borohydride or 2-aminoethanethiol, but these complex reactions do not produce clean organic products. A mechanism that includes nucleophile addition to the carbon βto the nitro group to generate a nitronate anion followed by protonation and nitrous acid elimination explains the observed products and labeling studies. These systematic studies give a better understanding of the release mechanisms of nitrogen oxide species from these compounds allowing for the design of more efficient therapeutics.<br /> (Copyright © 2021 Elsevier Ltd. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 1464-3405
- Volume :
- 48
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 34242759
- Full Text :
- https://doi.org/10.1016/j.bmcl.2021.128245