New cytotoxic mechanism of the bioreductive agent Tirapazamine (SR 4233) mediated by forming complex with copper
✍ Scribed by Peck-Sun Lin; Kwei-Chi Ho
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- English
- Weight
- 834 KB
- Volume
- 4
- Category
- Article
- ISSN
- 1065-7541
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✦ Synopsis
Tirapazamine (Tira, SR 4233), a Bioreductive agent, is highly toxic to cells under low oxygen conditions because it produces a toxic oxidizing radical intermediate. The mechanisms for its toxicity under aerobic conditions have not been fully established but involve reactive oxygen species production. In an earlier study, we observed that the cytotoxic effect of Tira under aerobic conditions varied in a series of experiments. We suspected that some unknown property or properties of this agent was responsible for causing the variation in our study. We have reason to believe that one property is due to Tira forming a complex with copper. Depending on the copper concentration, the cytotoxic potency of Tim under aerobic conditions may increase 2-to 10-fold while its effect under low oxygen conditions remains high. The Tim copper complex's stereochemistry likely has a ratio of 2 to 1. Several of the theoretical properties of this complex may lead to a new fundamental understanding of Tira effects in vitro and in vivo.