Discovery of novel N-substituted carbazoles as neuroprotective agents with potent anti-oxidative activity.

Abstract

Carbazole moiety is an important scaffold with a variety of biological applications, for example, anti-oxidative stress. Our previous synthesized carbazoles were screened for their neuroprotective properties against two individual oxidative stresses. Some of the new carbazole derivatives were observed with modest to good neuroprotective effects on neuronal cells HT22 against cell injury induced by glutamate or homocysteic acid (HCA). Substituents introduced to the carbazole ring system play crucial roles in their biological activities. In particular, a bulky group favors the neuroprotective activity of the compounds. One of the new compounds, 6, showed the best neuroprotective effects, which might result from its anti-oxidative activity with a GSH-independent mechanism. These findings might provide an alternative strategy for the development of novel carbazole derivatives for the treatment of CNS diseases such as Alzheimer's disease.

• Authors: Daqian Zhu, Meihui Chen, Min Li, Bingling Luo, Yang Zhao, Peng Huang, Fengtian Xue, Simona Rapposelli, Rongbiao Pi, Shijun Wen
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 68 Pg. 81-8 (Oct 2013) ISSN: 1768-3254 [Electronic] France
• PMID: 23973819 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Chemical References

• Antioxidants
• Carbazoles
• Neuroprotective Agents
• Reactive Oxygen Species
• Nitrogen

Topics

• Animals
• Antioxidants (chemical synthesis, chemistry, pharmacology)
• Carbazoles (chemical synthesis, chemistry, pharmacology)
• Cell Line
• Cell Survival (drug effects)
• Drug Discovery
• Mice
• Neuroprotective Agents (chemical synthesis, chemistry, pharmacology)
• Nitrogen (chemistry)
• Reactive Oxygen Species