SFB749 - The Two Faces of Potent Antitumor Duocarmycin-Based Drugs: A Structural Dissection Reveals Disparate Motifs for DNA versus Aldehyde Dehydrogenase 1 Affinity

The Two Faces of Potent Antitumor Duocarmycin-Based Drugs: A Structural Dissection Reveals Disparate Motifs for DNA versus Aldehyde Dehydrogenase 1 Affinity

16-May-2013

Tanja Wirth, Dr. Galina F. Pestel, Vanessa Ganal, Thomas Kirmeier, Dr. Ingrid Schuberth, Theo Rein, Professor Lutz F. Tietze and Professor Stephan A. Sieber

Angew. Chem.Int. Ed., 2013, 52 (27), 6921–6925

Angew. Chem. Int. Ed.

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.