A structurally simplified analogue of geldanamycin exhibits neuroprotective activity

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

doi:10.1021/ml400207m

A structurally simplified analogue of geldanamycin exhibits neuroprotective activity

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

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

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 language	English (US)
Pages (from-to)	953-957
Number of pages	5
Journal	ACS Medicinal Chemistry Letters
Volume	4
Issue number	10
DOIs	https://doi.org/10.1021/ml400207m
State	Published - Oct 10 2013

Keywords

Geldanamycin
lipid peroxidation
mitochondria
oxidative stress

ASJC Scopus subject areas

Biochemistry
Drug Discovery
Organic Chemistry

Access to Document

10.1021/ml400207m

Cite this

@article{7b3f69018dac4cf3af841c0d45b37b7d,

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.",

keywords = "Geldanamycin, lipid peroxidation, mitochondria, oxidative stress",

author = "Madathil, {Manikandadas M.} and Omar Khdour and Jennifer Jaruvangsanti and Sidney Hecht",

year = "2013",

month = oct,

day = "10",

doi = "10.1021/ml400207m",

language = "English (US)",

volume = "4",

pages = "953--957",

journal = "ACS Medicinal Chemistry Letters",

issn = "1948-5875",

publisher = "American Chemical Society",

number = "10",

}

TY - JOUR

T1 - A structurally simplified analogue of geldanamycin exhibits neuroprotective activity

AU - Madathil, Manikandadas M.

AU - Khdour, Omar

AU - Jaruvangsanti, Jennifer

AU - Hecht, Sidney

PY - 2013/10/10

Y1 - 2013/10/10

N2 - 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.

AB - 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.

KW - Geldanamycin

KW - lipid peroxidation

KW - mitochondria

KW - oxidative stress

UR - http://www.scopus.com/inward/record.url?scp=84885442630&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84885442630&partnerID=8YFLogxK

U2 - 10.1021/ml400207m

DO - 10.1021/ml400207m

M3 - Article

AN - SCOPUS:84885442630

SN - 1948-5875

VL - 4

SP - 953

EP - 957

JO - ACS Medicinal Chemistry Letters

JF - ACS Medicinal Chemistry Letters

IS - 10

ER -

A structurally simplified analogue of geldanamycin exhibits neuroprotective activity

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this