This research was funded by the Foundation for Research, Science and Technology, NZ, and Proacta. We thank Sisira Kumara, Maruta Boyd, Sally Bai, Wouter van Leeuwen, and Caroline McCulloch for technical assistance.
Selective Treatment of Hypoxic Tumor Cells In Vivo: Phosphate Pre-Prodrugs of Nitro Analogues of the Duocarmycins†
Article first published online: 17 FEB 2011
Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Angewandte Chemie International Edition
Volume 50, Issue 11, pages 2606–2609, March 7, 2011
How to Cite
Tercel, M., Atwell, G. J., Yang, S., Ashoorzadeh, A., Stevenson, R. J., Botting, K. J., Gu, Y., Mehta, S. Y., Denny, W. A., Wilson, W. R. and Pruijn, F. B. (2011), Selective Treatment of Hypoxic Tumor Cells In Vivo: Phosphate Pre-Prodrugs of Nitro Analogues of the Duocarmycins. Angew. Chem. Int. Ed., 50: 2606–2609. doi: 10.1002/anie.201004456
- Issue published online: 2 MAR 2011
- Article first published online: 17 FEB 2011
- Manuscript Revised: 2 JAN 2011
- Manuscript Received: 21 JUL 2010
- Foundation for Research, Science and Technology, NZ
- antitumor agents;
Hitting the hypoxic target: Combining a nitro prodrug with a water-soluble phosphate converts duocarmycin analogues from highly toxic DNA-alkylating agents to highly selective antitumor compounds. These prodrugs (see scheme) have outstanding activity against hypoxic tumor cells in vivo, cells which are usually considered the most resistant to conventional therapy.