A structurally simplified analogue of geldanamycin exhibits neuroprotective activity

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

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)953-957
Number of pages5
JournalACS Medicinal Chemistry Letters
Volume4
Issue number10
DOIs
StatePublished - Oct 10 2013

Fingerprint

Friedreich Ataxia
Lymphocytes
Cytoprotection
Mitochondrial Membrane Potential
Cytotoxicity
Membrane Lipids
Lipid Peroxidation
Toxicity
Membranes
Lipids
geldanamycin
Neuroprotection

Keywords

  • Geldanamycin
  • lipid peroxidation
  • mitochondria
  • oxidative stress

ASJC Scopus subject areas

  • Organic Chemistry
  • Drug Discovery
  • Biochemistry

Cite this

A structurally simplified analogue of geldanamycin exhibits neuroprotective activity. / Madathil, Manikandadas M.; Khdour, Omar; Jaruvangsanti, Jennifer; Hecht, Sidney.

In: ACS Medicinal Chemistry Letters, Vol. 4, No. 10, 10.10.2013, p. 953-957.

Research output: Contribution to journalArticle

Madathil, Manikandadas M. ; Khdour, Omar ; Jaruvangsanti, Jennifer ; Hecht, Sidney. / A structurally simplified analogue of geldanamycin exhibits neuroprotective activity. In: ACS Medicinal Chemistry Letters. 2013 ; Vol. 4, No. 10. pp. 953-957.
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