A structurally simplified analogue of geldanamycin exhibits neuroprotective activity

Manikandadas M. Madathil, Omar Khdour, Jennifer Jaruvangsanti, Sidney Hecht

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


The syntheses of a structurally simplified geldanamycin analogue 2 and two related compounds are described. Compound 2 conferred cytoprotection and quenched ROS and lipid peroxidation in a dose-dependent manner in Friedreich's ataxia (FRDA) lymphocytes at low micromolar concentrations. It also prevented ROS-induced damage of cellular lipid membranes and maintained the mitochondrial membrane potential of FRDA lymphocytes. In addition, 2 did not inhibit Hsp90 when tested at micromolar concentrations, exhibited no cytotoxicity, and afforded neuroprotection to differentiated SH-SY5Y cells under conditions of Aβ-induced cell toxicity.

Original languageEnglish (US)
Pages (from-to)953-957
Number of pages5
JournalACS Medicinal Chemistry Letters
Issue number10
StatePublished - Oct 10 2013


  • Geldanamycin
  • lipid peroxidation
  • mitochondria
  • oxidative stress

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry


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