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Updated: Apr 28, 2026
Caenorhabditis elegans as a Model System for Discovering Bioactive Compounds Against Polyglutamine-Mediated Neurotoxicity
Published on: September 21, 2021
A structurally simplified analogue of geldanamycin exhibits neuroprotective activity
Manikandadas M Madathil1, Omar M Khdour1, Jennifer Jaruvangsanti1
1Center for BioEnergetics, Biodesign Institute, and Department of Chemistry and Biochemistry, Arizona State University , Tempe, Arizona 85287-2904, United States.
Abstract:
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.
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