Synthesis and initial in vitro evaluations of novel antioxidant aroylhydrazone iron chelators with increased stability against plasma hydrolysis
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
21214215
DOI
10.1021/tx100359t
Knihovny.cz E-resources
- MeSH
- Aldehydes blood chemistry pharmacology MeSH
- Antioxidants chemistry metabolism pharmacology MeSH
- Cell Line MeSH
- Iron Chelating Agents chemical synthesis metabolism pharmacology MeSH
- Hydrazones blood chemistry pharmacology MeSH
- Hydrolysis MeSH
- Hydroxyl Radical toxicity MeSH
- Rabbits MeSH
- Rats MeSH
- Oxidative Stress MeSH
- Drug Stability MeSH
- Animals MeSH
- Check Tag
- Rabbits MeSH
- Rats MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Aldehydes MeSH
- Antioxidants MeSH
- Iron Chelating Agents MeSH
- Hydrazones MeSH
- Hydroxyl Radical MeSH
- salicylaldehyde isonicotinoyl hydrazone MeSH Browser
Oxidative stress is known to contribute to a number of cardiovascular pathologies. Free intracellular iron ions participate in the Fenton reaction and therefore substantially contribute to the formation of highly toxic hydroxyl radicals and cellular injury. Earlier work on the intracellular iron chelator salicylaldehyde isonicotinoyl hydrazone (SIH) has demonstrated its considerable promise as an agent to protect the heart against oxidative injury both in vitro and in vivo. However, the major limitation of SIH is represented by its labile hydrazone bond that makes it prone to plasma hydrolysis. Hence, in order to improve the hydrazone bond stability, nine compounds were prepared by a substitution of salicylaldehyde by the respective methyl- and ethylketone with various electron donors or acceptors in the phenyl ring. All the synthesized aroylhydrazones displayed significant iron-chelating activities and eight chelators showed significantly higher stability in rabbit plasma than SIH. Furthermore, some of these chelators were observed to possess higher cytoprotective activities against oxidative injury and/or lower toxicity as compared to SIH. The results of the present study therefore indicate the possible applicability of several of these novel agents in the prevention and/or treatment of cardiovascular disorders with a known (or presumed) role of oxidative stress. In particular, the methylketone HAPI and nitro group-containing NHAPI merit further in vivo investigations.
References provided by Crossref.org
