The Two Faces of Potent Antitumor Duocarmycin-Based Drugs: A Structural Dissection Reveals Disparate Motifs for DNA versus Aldehyde Dehydrogenase1 Affinity

Duocarmycin-derived seco-cyclopropabenzindole (CBI) drugs have been shown to bind DNA and an aldehyde dehydrogenase (ALDH1A1) in lung cancer cells. The removal of the DNA-binding indole moiety results in a CBI compound that does not bind to DNA in whole cells but still exhibits remarkable cytotoxici...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2013-07, Vol.52 (27), p.6921-6925
Main Authors: Wirth, Tanja, Pestel, Galina F, Ganal, Vanessa, Kirmeier, Thomas, Schuberth, Ingrid, Rein, Theo, Tietze, Lutz F, Sieber, Stephan A
Format: Article
Language:English
Subjects:
Affinity
Aldehydes
Cancer
Deoxyribonucleic acid
Dissection
Drugs
Indoles
Lungs
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Summary:Duocarmycin-derived seco-cyclopropabenzindole (CBI) drugs have been shown to bind DNA and an aldehyde dehydrogenase (ALDH1A1) in lung cancer cells. The removal of the DNA-binding indole moiety results in a CBI compound that does not bind to DNA in whole cells but still exhibits remarkable cytotoxicity. This CBI compound has an increased affinity for ALDH1A1. Rh=rhodamine.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201208941