Topic
Streptonigrin
About: Streptonigrin is a research topic. Over the lifetime, 372 publications have been published within this topic receiving 11182 citations. The topic is also known as: bruneomycin & nigrin.
Papers published on a yearly basis
1 / 2
Papers
Journal Article•
TL;DR: It is proposed that the intracellular activation of these quinone anticancer drugs to a free radical state may be primary to their cytotoxic activity.
Abstract: The highly active, quinone-containing anticancer drugs, Adriamycin, daunorubicin, carminomycin, rubidazone, nogalamycin, aclacinomycin A, and steffimycin (benzanthraquinones); mitomycin C and streptonigrin (N-heterocyclic quinones); and lapachol (naphthoquinone) interact with mammalian microsomes and function as free radical carriers. These quinone drugs augment the flow of electrons from reduced nicotinamide adenine dinucleotide phosphate to molecular oxygen as measured by enhanced reduced nicotinamide adenine dinucleotide phosphate oxidation and oxygen consumption. This reaction is catalyzed by microsomal protein and produces a free radical intermediate form of the drugs as determined by electron paramagnetic resonance spectroscopy. Microsomes from mouse and rat liver, heart, lung, and spleen and mouse L1210 and P388 tumors all catalyze the augmented oxygen consumption. Apparent Km values determined with normal rat liver microsomes range from 0.49 × 10-4m for steffimycin to 13.4 × 10-4m for lapachol. Since SKF 525A and carbon monoxide have little effect on this reaction, cytochrome P-450 is probably not involved. Several nonquinone anticancer agents were tested and were found inactive in the system. Since quinone anticancer drugs are associated with chromosomal damage that appears to be dependent on metabolic activation of these drugs, we propose that the intracellular activation of these drugs to a free radical state may be primary to their cytotoxic activity. As free radicals, these drugs, because of their high affinity and selective binding to nucleic acids, have the potential to be “site-specific free radicals” that bind to DNA or RNA and either react directly or generate oxygen-dependent free radicals such as superoxide radical or hydroxyl radical to cause the damage associated with their cytotoxic actions.
685 citations
TL;DR: The effect of alloxan appeared paradoxical in that it increased cyanide-resistant respiration without significantly increasing the cell content of the manganese-superoxide dismutase and with only a small effect on the level of catalase.
612 citations
TL;DR: It is postulate that the formation of the "site-specific free radical/ intermediate is central to the cytotoxic action of these antibiotics.
Abstract: With NADPH as the electron donor, rat liver NADPH cytochrome P-450 reductase (NADPH:ferricytochrome oxidoreductase, EC 1.6.2.4) catalyzes the single-electron reduction of several quinone antibiotics to a semiquinone or free radical state. The benzanthraquinones adriamycin, daunorubicin, carminomycin, 7-O-methylnogalarol, and aclacinomycin A and the N-heterocyclic quinones streptonigrin and mitomycin C are activated to free radical intermediates which can transfer their single electron to molecular oxygen to form superoxide. The overall Km range for this electron transfer is 0.4 to 42.1 X 10(-4) M. We postulate that the formation of the "site-specific free radical/ intermediate is central to the cytotoxic action of these antibiotics.
525 citations
TL;DR: Observations lend support to the hypothesis that O(2) (-) is an important agent of oxygen toxicity and that superoxide dismutase functions to blunt the threat posed by this reactive radical.
Abstract: Oxygen caused an increase in the amount of superoxide dismutase in Escherichia coli B but not in Bacillus subtilis. E. coli B cells, induced by growth under 100% O2, were much more resistant to the lethal effects of 20 atm of O2 than were cells which contained the low uninduced level of this enzyme. In contrast, B. subtilis, which could not respond to O2 by increasing its content of superoxide dismutase, remained equally sensitive to hyperbaric O2 whether grown under 100% O2 or areobically. The catalase in these organisms exhibited a reciprocal response to oxygen. Thus, the catalase of E. coli B was not induced by O2, whereas that of B. subtilis was so induced. These results are consistent with the view that superoxide dismutase is an important component of the defenses of these organisms against the toxicity of oxygen, whereas their catalases are of secondary importance in this respect. The ability of streptonigrin to generate O2−, by a cycle of reduction followed by spontaneous reoxidation, has been verified in vitro. It is further observed that E. coli B which contain the high induced level of superoxide dismutase were more resistant to the lethality of this antibiotic, in the presence of oxygen, than were E. coli B which contained the low uninduced level of this enzyme. This difference between induced and uninduced cells was eliminated by the removal of O2. These results are consistent with the proposal that the enhanced lethality of streptonigrin under aerobic conditions may relate to its in vivo generation of O2− by a cycle of reduction and spontaneous reoxidation. In toto, these observations lend support to the hypothesis that O2− is an important agent of oxygen toxicity and that superoxide dismutase functions to blunt the threat posed by this reactive radical.
280 citations
Book•
1 Jan 1979
TL;DR: The chiral stationary phase for high-performance liquid chromatography of nogalamycin showed good chiral recognition ability towards various racemates, including polypeptide A and polymethine.
Abstract: Streptozocin. Pyrrolo (1,4) Benzodiazepines. Saframycins, Renieramycins, and Safracins. Naphthyridinomycin, Cyanocyclines, and Quinocarcin. CC-1065. Nogalamycin and Related Compounds. Streptonigrin and Lavendamycin. Index.
257 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2021 | 2 |
| 2020 | 7 |
| 2019 | 3 |
| 2018 | 5 |
| 2017 | 3 |
| 2016 | 6 |