Synthesis and characterization of novel indole derivatives reveal improved therapeutic agents for treatment of ischemia/reperfusion (I/R) injury.

Abstract

To develop more potent therapeutic agents with therapeutic efficacy for ischemia/reperfusion (I/R) injury, we linked an antiinflammatory moiety (1,3-dioxane derivative) to the key pharmacophoric moiety of melatonin. We hypothesized that the resulting new indole derivatives might induce a synergistic protection against oxidative damage associated with I/R injury. Our results indicate that one of these indole derivatives (7) manifests potent antiinflammatory antioxidant effects and exerts a protective effect against skeletal muscle injury and associated lung injury following limb I/R in rats.

• Authors: Wei Bi, Yue Bi, Ping Xue, Yanrong Zhang, Xiang Gao, Zhibo Wang, Meng Li, Michèle Baudy-Floc'h, Nathaniel Ngerebara, K Michael Gibson, Lanrong Bi
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 53 Issue 18 Pg. 6763-7 (Sep 23 2010) ISSN: 1520-4804 [Electronic] United States
• PMID: 20731361 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Antioxidants
• Free Radical Scavengers
• Indoles

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (chemical synthesis, chemistry, pharmacology)
• Antioxidants (chemical synthesis, chemistry, pharmacology)
• Capillary Permeability
• Free Radical Scavengers (chemical synthesis, chemistry, pharmacology)
• Hindlimb (blood supply)
• Indoles (chemical synthesis, chemistry, pharmacology)
• Inflammation (drug therapy)
• Lipid Peroxidation (drug effects)
• Lung Injury (drug therapy, metabolism, pathology)
• Mice
• Muscle, Skeletal (blood supply, drug effects, pathology)
• PC12 Cells
• Rats
• Reperfusion Injury (drug therapy, metabolism, pathology)
• Structure-Activity Relationship