A Structurally Simplified Analogue of Geldanamycin Exhibits Neuroprotective Activity

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 preve...

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Bibliographic Details
Published in:ACS medicinal chemistry letters 2013-10, Vol.4 (10), p.953-957
Main Authors: Madathil, Manikandadas M, Khdour, Omar M, Jaruvangsanti, Jennifer, Hecht, Sidney M
Format: Article
Language:English
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Letter
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Summary: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.
ISSN:1948-5875
1948-5875
DOI:10.1021/ml400207m