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A structurally simplified analogue of geldanamycin exhibits neuroprotective activity.

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 A?-induced cell toxicity.

SUBMITTER: Madathil MM

PROVIDER: S-EPMC4027499 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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A structurally simplified analogue of geldanamycin exhibits neuroprotective activity.

Madathil Manikandadas M MM Khdour Omar M OM Jaruvangsanti Jennifer J Hecht Sidney M SM

ACS medicinal chemistry letters 20130725 10

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 concentratio ...[more]

PMID: 24900591

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