Aminopropyl carbazole analogues as potent enhancers of neurogenesis

Bioorg Med Chem. 2013 Nov 15;21(22):7165-74. doi: 10.1016/j.bmc.2013.08.066. Epub 2013 Sep 8.

Abstract

Neural stem cells are multipotent and self-renewing cells that can differentiate into new neurons and hold great promise for treating various neurological disorders including multiple sclerosis, Parkinson's disease, and Alzheimer's disease. Small molecules that can trigger neurogenesis and neuroprotection are particularly useful not only because of their therapeutic implications but also because they can provide an invaluable tool to study the mechanisms of neurogenesis. In this report, we have developed and screened 25 aminopropyl carbazole derivatives that can enhance neurogenesis of cultured neural stem cells. Among these analogues, compound 9 demonstrated an excellent proneurogenic and neuroprotective activity with no apparent toxicity. We believe that compound 9 can serve as an excellent lead to develop various analogues and to study the underlying mechanisms of neurogenesis.

Keywords: Aminopropyl carbazole; Neural stem cells; Neurodegenerative diseases; Neurogenesis; Neuroprotective agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbazoles / chemical synthesis
  • Carbazoles / chemistry*
  • Carbazoles / pharmacology*
  • Cell Survival / drug effects
  • Neural Stem Cells / cytology*
  • Neurogenesis / drug effects*
  • Neuroprotective Agents / chemical synthesis
  • Neuroprotective Agents / chemistry*
  • Neuroprotective Agents / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Structure-Activity Relationship
  • Sulfonamides / chemical synthesis
  • Sulfonamides / chemistry*
  • Sulfonamides / pharmacology*

Substances

  • Carbazoles
  • N-(3-(3,6-dibromo-9H-carbazol-9-yl)-2-hydroxypropyl)-N-(3-methoxyphenyl)-4-methylbenzenesulfonamide
  • Neuroprotective Agents
  • Sulfonamides
  • carbazole