| Title |
7-Nitro-4-(phenylthio)benzofurazan is a potent generator of superoxide and hydrogen peroxide
|
|---|---|
| Published in |
Archives of Toxicology, June 2012
|
| DOI | 10.1007/s00204-012-0872-9 |
| Pubmed ID | |
| Authors |
Eric V. Patridge, Emma S. E. Eriksson, Philip G. Penketh, Raymond P. Baumann, Rui Zhu, Krishnamurthy Shyam, Leif A. Eriksson, Alan C. Sartorelli |
| Abstract |
Here, we report on 7-nitro-4-(phenylthio)benzofurazan (NBF-SPh), the most potent derivative among a set of patented anticancer 7-nitrobenzofurazans (NBFs), which have been suggested to function by perturbing protein-protein interactions. We demonstrate that NBF-SPh participates in toxic redox-cycling, rapidly generating reactive oxygen species (ROS) in the presence of molecular oxygen, and this is the first report to detail ROS production for any of the anticancer NBFs. Oxygraph studies showed that NBF-SPh consumes molecular oxygen at a substantial rate, rivaling even plumbagin, menadione, and juglone. Biochemical and enzymatic assays identified superoxide and hydrogen peroxide as products of its redox-cycling activity, and the rapid rate of ROS production appears to be sufficient to account for some of the toxicity of NBF-SPh (LC(50) = 12.1 μM), possibly explaining why tumor cells exhibit a sharp threshold for tolerating the compound. In cell cultures, lipid peroxidation was enhanced after treatment with NBF-SPh, as measured by 2-thiobarbituric acid-reactive substances, indicating a significant accumulation of ROS. Thioglycerol rescued cell death and increased survival by 15-fold to 20-fold, but pyruvate and uric acid were ineffective protectants. We also observed that the redox-cycling activity of NBF-SPh became exhausted after an average of approximately 19 cycles per NBF-SPh molecule. Electrochemical and computational analyses suggest that partial reduction of NBF-SPh enhances electrophilicity, which appears to encourage scavenging activity and contribute to electrophilic toxicity. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 13 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| India | 1 | 8% |
| Unknown | 12 | 92% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 3 | 23% |
| Student > Ph. D. Student | 3 | 23% |
| Professor | 2 | 15% |
| Librarian | 1 | 8% |
| Other | 1 | 8% |
| Other | 0 | 0% |
| Unknown | 3 | 23% |
| Readers by discipline | Count | As % |
|---|---|---|
| Chemistry | 4 | 31% |
| Agricultural and Biological Sciences | 3 | 23% |
| Psychology | 1 | 8% |
| Medicine and Dentistry | 1 | 8% |
| Social Sciences | 1 | 8% |
| Other | 0 | 0% |
| Unknown | 3 | 23% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 18 July 2012.
All research outputs
#17,659,617
of 22,668,244 outputs
Outputs from Archives of Toxicology
#2,139
of 2,630 outputs
Outputs of similar age
#124,052
of 166,900 outputs
Outputs of similar age from Archives of Toxicology
#12
of 12 outputs
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