Chemotherapeutic agents such as nitrogen mustards and cisplatin work by inducing DNA interstrand cross-links. This stops DNA replication and transcription, and ultimately kills the cell. These agents exhibit severe host toxicity due to their poor selectivity toward cancer cells. Anticancer prodrugs that target the biochemical alterations unique to cancer cells could reduce toxicity and increase therapeutic activity.
Xiaohua Peng and colleagues, University of Wisconsin, Milwaukee, USA, have developed the first anticancer prodrugs that are activated by the high level of reactive oxygen species, such as H2O2, found in cancer cells. The prodrugs consist of nitrogen mustard coupled with an arylboronate or boronic acid. In the presence of H2O2, the C–B bond was cleaved and the active DNA cross-linking agent was released. The compounds showed 60–90 % inhibition toward various cancer cells, while normal lymphocytes were not affected.
- Hydrogen Peroxide Inducible DNA Cross-Linking Agents: Targeted Anticancer Prodrugs
Y. Kuang, K. Balakrishnan, V. Gandhi, X. Peng,
J. Am. Chem. Soc. 2011.