title: 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 Aβ-induced cell toxicity.
authors.affiliation: Center for BioEnergetics, Biodesign Institute, and Department of Chemistry and Biochemistry, Arizona State University , Tempe, Arizona 85287-2904, United States.
authors.forename: Manikandadas M
authors.initials: MM
authors.lastname: Madathil
authors.affiliation: Center for BioEnergetics, Biodesign Institute, and Department of Chemistry and Biochemistry, Arizona State University , Tempe, Arizona 85287-2904, United States.
authors.forename: Omar M
authors.initials: OM
authors.lastname: Khdour
authors.affiliation: Center for BioEnergetics, Biodesign Institute, and Department of Chemistry and Biochemistry, Arizona State University , Tempe, Arizona 85287-2904, United States.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Jaruvangsanti
authors.affiliation: Center for BioEnergetics, Biodesign Institute, and Department of Chemistry and Biochemistry, Arizona State University , Tempe, Arizona 85287-2904, United States.
authors.forename: Sidney M
authors.initials: SM
authors.lastname: Hecht
keywords: Geldanamycin; lipid peroxidation; mitochondria; oxidative stress