Hypoxia activated prodrugs of a 9-aza-anthrapyrazole derivative that has promising anticancer activity

  • J Med Chem. 2011 Dec 8;54(23):8224-7. doi: 10.1021/jm200984x.
Mohammad H El-Dakdouki  1 ,  Nicholas Adamski ,  Lecia Foster ,  Miles P Hacker ,  Paul W Erhardt
Affiliations
  • 1. Center for Drug Design and Development, College of Pharmacy and Pharmaceutical Sciences, The University of Toledo, Toledo, Ohio 43606, United States.
PMID: 22011244 DOI: 10.1021/jm200984x
Abstract

Mono- and bis-N-oxides of a 9-aza-anthrapyrazole derivative having two 2-(dimethylamino)ethyl appendages were prepared by using a mild oxaziridine reagent. Biochemical and Cell Culture assays indicate that the bis-oxide is an inactive prodrug that readily converts to the active parent molecule under hypoxic conditions that are analogous to those present within certain tumors.